Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Author index

Page Path
HOME > Browse > Author index
Search
Kwang Woo Lee  (Lee KW) 44 Articles
Depression and Self-care Behavior in Patients with Diabetes Mellitus.
Su Yoen Kim, Jae Ho Lee, Ha Neul Kim, Dong Kyu Kim, Young Na, Guil Sun Kim, Mee Kyoung Kim, Ki Hyun Baek, Moo IL Kang, Kwang Woo Lee, Ki Ho Song
Korean Diabetes J. 2009;33(5):432-438.   Published online October 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.5.432
  • 2,942 View
  • 59 Download
  • 7 Crossref
AbstractAbstract PDF
BACKGROUND
Depression is known to be a risk factor for type 2 diabetes mellitus. Conversely, diabetes is also a risk factor for depression, and patients with diabetes have nearly twice the risk of comorbid depression as the general population. Depression in patients with diabetes may cause poor clinical outcomes through lower adherence to self-care activities such as exercise, diet control, and glucose monitoring. Furthermore, diabetic patients with depression are more likely to suffer from microvascular or macrovascular complications. We explored the prevalence of major depressive disorder in Korean diabetic patients and its impact on self-care activities and glucose control. METHODS: We surveyed depressive symptoms and self-care activities in 191 type 2 diabetic patients from the outpatient clinic of the St. Mary's hospital. Two questionnaires were used for assessment, the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) and the Summary of Diabetes Self-Care Activities (SDSCA). RESULTS: Of the 191 respondents who completed questionnaires, 39 (20.4%) patients were categorized as having major depressive disorder. Among the depressed patients, only six (15.3%) had been previously evaluated and managed for their psychiatric problems. The incidence of depression was significantly higher in female diabetic patients compared to patients without depression (74.4% vs. 45.4%, P<0.001). Patients with depression showed significantly poorer diet control (18.5 vs. 15.9, P = 0.046) and less glucose monitoring (4.1 vs. 2.7, P = 0.047). However, there were no differences in exercise, foot care, or smoking status between the two groups. Additionally, metabolic parameters such as HbA1C and lipid profile were not significantly different between the two groups. CONCLUSION: Many diabetic patients are suffering from depression and exhibit poorer self-care activities than patients without depression. Identifying and managing depressed diabetic patients may help improve their self-care activities.

Citations

Citations to this article as recorded by  
  • The Effects of the 2030 Diabetes Camp Program on Depression, Anxiety, and Stress in Diabetic Patients
    Jin Hee Jung, Jung Hwa Lee
    The Journal of Korean Diabetes.2019; 20(3): 194.     CrossRef
  • Association of Resilience and Depression with Self-care Competence in Adult Patients with Diabetes Mellitus
    Youngrye Park, Eun Hee Jang, Ji Ok Kim
    Korean Journal of Adult Nursing.2018; 30(5): 555.     CrossRef
  • Health-Related Quality-of-Life and Diabetes Self-Care Activity in Elderly Patients with Diabetes in Korea
    Hacksun Kim, Kisook Kim
    Journal of Community Health.2017; 42(5): 998.     CrossRef
  • Associations between Smoking, Drinking and Depression among Korean Adults: The 5th Korea National Health and Nutrition Examination Survey
    Sun Mi Park, Mi Ah Han, Jong Park, So Yeon Ryu, Seong Woo Choi, Hwan Ho Shin, Mi Hyun Joo
    Korean Journal of Health Promotion.2016; 16(2): 111.     CrossRef
  • Diabetes and Depressive Symptoms in Korean Women: The Fifth Korean National Health and Nutrition Examination Survey (2010-2011)
    Han Na Sung, Hong Seok Chae, Eung Soo Kim, Jong Sung Kim
    Korean Journal of Family Medicine.2014; 35(3): 127.     CrossRef
  • Effects of Abdominal Circumference, Blood Lipids and Blood Pressure according to Diabetes with VO2peak
    Sang-Nam Nam, Jung-Beom Park, Hyoung-Ju Lee
    The Journal of the Korea Contents Association.2012; 12(12): 363.     CrossRef
  • Effects of a Cardiovascular Risk Reduction Intervention With Psychobehavioral Strategies for Korean Adults With Type 2 Diabetes and Metabolic Syndrome
    Chun-Ja Kim, Dae-Jung Kim, Hyung-Ran Park
    Journal of Cardiovascular Nursing.2011; 26(2): 117.     CrossRef
The Classification of Diabetic Patients Presenting Diabetic Ketoacidosis: The Characteristics of Fulminant Type 1 Diabetes.
Eun Hee Jang, Jeong Eun Yi, Seung Jae Lee, Sang Hoon Chun, Ki Hyun Baek, Ki Ho Song, Soon Jib Yoo, Jong Min Lee, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Mee Kyung Kim
Korean Diabetes J. 2008;32(5):428-434.   Published online October 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.5.428
  • 3,032 View
  • 61 Download
  • 2 Crossref
AbstractAbstract PDF
BACKGROUND
The aim of the study was to classify newly diagnosed diabetic patients who initially presented with diabetic ketoacidosis (DKA) into specific types of diabetes and to describe the clinical and biochemical characteristics of patients with fulminant type 1 DM in Korea. METHODS: Using data from 4 hospitals of CMC from 1 January 1999 to 1 March 2008, we identified all patients who manifested DKA when they were first diagnosed as diabetes. Clinical and laboratory data were reviewed from medical records. RESULTS: We identified 51 newly diagnosed diabetic patients manifested DKA. Among them, 14 (27.4%) patients were classified as autoimmune type 1 DM, 8 (15.7%) as antibody negative type 1 DM, 5 (9.8%) as fulminant type 1, 16 (31.4%) as type 2 DM and 8 (15.7%) as secondary DM. Five patients who fulfilled the criteria of fulminant type 1 DM were older (32.2 +/- 10.7 vs. 15.7 +/- 4.4 years, P = 0.010), had shorter duration of symptoms (4.2 +/- 2.7 vs.16.7 +/- 15.2 days, P = 0.014) and lower stimulated C-peptide levels (0.1 +/- 0.0 vs. 0.7 +/- 0.6 ng/mL, P = 0.050) compared with patients with autoimmune type 1 DM. CONCLUSION Newly diagnosed diabetic patients presenting with DKA composed of heterogenous types of diabetes. The prevalence of fulminant type 1 diabetes among them was 9.8% and the clinical and biochemical characteristics of these patients were different from those of autoimmune type 1 DM.

Citations

Citations to this article as recorded by  
  • A Case of Severe Diabetic Ketoacidosis in a Child with Type 2 Diabetes
    Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
    Journal of Korean Society of Pediatric Endocrinology.2011; 16(1): 46.     CrossRef
  • A Case of Fulminant Type 1 Diabetes Mellitus Complicated with Ischemic Ileitis
    Se-Won Oh, Ju-Ri Park, Yun-Jeong Lee, Hee-Yeong Kim, Ji-A Seo, Nan-Hee Kim, Kyung-Mook Choi, Sei-Hyun Baik, Dong-Seop Choi, Sin-Gon Kim
    Journal of Korean Endocrine Society.2009; 24(2): 116.     CrossRef
The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells.
Ji Hyun Kim, Ji Won Kim, Sung Yoon Jeon, Heon Seok Park, Dong Sik Ham, Young Hye You, Seung Hwan Lee, Jae Hyoung Cho, Mi Ja Kang, Kang Woo Lee, Hyuk Sang Kwon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Sung Koo Kang, Ho Young Son
Korean Diabetes J. 2008;32(2):102-111.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.102
  • 2,850 View
  • 36 Download
AbstractAbstract PDF
BACKGROUND
Insulin receptor substrate 2 (IRS-2) is a key regulator of beta cell proliferation and apoptosis. This study was aimed to investigate effect of the glucolipotoxicity on apoptosis in INS-1 cell, and the effect of Exendin-4, a GLP-1 receptor agonist, on IRS-2 expression in the glucolipotoxicity induced INS-1 cell. The goal was to discover the new action mechanism and function of Exendin-4 in beta cell apoptosis. METHOD: INS-1 cells were cultured in glucolipotoxic condition for 2, 4 or 6 days and were categorized as G groups. Another group in which 50 nM Exendin-4 was added to INS-1 cells, cultured in glucolipotoxic condition, were named as Ex-4 groups. We investigated the expression of IRS-2 by RT-PCR, phosphorylated IRS-2 and phosphorylated Akt protein levels by western blot. We measured the apoptosis ratio of INS-1 cell in glucolipotoxic condition by TUNEL staining in both groups. RESULT: IRS-2 expression of INS-1 cells decreased with correlation to the time of exposure to glucolipotoxic condition. pIRS-2 and pAkt protein levels decreased in the similar pattern in glucolipotoxicity group. However, this effect of glucolipotoxicity on INS-1 cell was inhibited by the Exendin-4 treatment. In the Ex-4 groups, IRS-2 expression, pIRS-2 and pAkt protein levels remained at the similar level to low glucose condition state. Also, apoptosis induced by glucolipotoxicity was suppressed by Exendin-4 treatment significantly. CONCLUSION: We showed that the long-term treatment of Exendin-4 inhibited the apoptosis of beta cells significantly in glucolipotoxic condition and that this effect of Exendin-4 was related with IRS-2 and Akt among the beta cell's intracellular signal transduction pathway.
The Differences of Circulating Adiponectin Levels and Multimerization According to Obesity in Type 2 Diabetes Mellitus of Men.
Sang Ah Chang, Ho Young Son, Jung Min Lee, Tae Seo Sohn, Hyuk Sang Kwon, Hyun Shik Son, Kun Ho Yoon, Hee Seung Kim, Bong Yun Cha, Kwang Woo Lee
Korean Diabetes J. 2007;31(3):243-252.   Published online May 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.3.243
  • 2,053 View
  • 19 Download
AbstractAbstract PDF
BACKGROUND
Adiponectin is adipose tissue derived hormone, which has been shown to play an important role in the regulation of glucose and lipid metabolism. Low adiponectin levels are associated with obesity and diabetes and coronary artery disease. In addition to adiponectin level, the adiponectin multimerization and its ratio to total adiponectin have also affect on metabolic risk factors and insulin resistance. However, the adiponectin multimerization pattern in type 2 diabetes of Korean has not been established. We investigated adiponectin levels and adiponectin multimerization pattern according to obesity in type 2 diabetes males of Korean. METHOD: The subjects of this study were 86 of diabetes patients and 89 of control subjects whose fasting blood glucose was below 110 mg/dL. They were divided into two subgroup, non-obese and obese, according to BMI (non-obese 25 < BMI). Anthropometric parameter and other metabolic risk factors were measured. Insulin resistance was presented by HOMA-IR. Plasma adiponectin level was measured by radioimmunoassay method. Adiponectin multimerization was fractionated by SDS-PAGE under non-reducing and non-heat denaturing state and performed immunoblotting. RESULT: Serum adiponectin levels were significantly reduced in obese than non obese group in diabetes patients (7.73 +/- 5.2 versus 12.56 +/- 8 microgram/mL, P = 0.003). Correlational analyses demonstrated that BMI, body weight, waist circumference, diastolic pressure, glucose and height correlated significantly with adiponectin levels in the diabetes patients. The HOMA-IR did not affect the plasma adiponectin levels in diabetic patients. There were no differences in adiponectin multimerization distribution and ratio between obese and non-obese group in the diabetes, however middle molecular weight multimers (MMW, ~110~160 Kda, hexamer) ratio in the control subjects were significantly reduced in obese group than non-obese group (49 +/- 9 versus 56 +/- 11%, P < 0.05). CONCLUSION: The adipoenctin levels were lower in obese than non-obese group of diabetes males in Korea. Aiponectin levels correlated with BMI and weight but not insulin resistance. The differences of adiponectin multimerization distribution and ratio between obese and non-obese group in diabetes were not detected.
Differentiation of Pancreatic beta Cells from Human Pancreatic Duct Cells Derived from a Partial Pancreas Tissue.
Ki Ho Song, Myung Mee Kim, Min Kyung Lee, Gyeong Ryul Ryu, Seung Hyun Ko, Sung Dae Moon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Hyung Min Chin
Korean Diabetes J. 2007;31(3):236-242.   Published online May 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.3.236
  • 2,300 View
  • 25 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Despite a recent breakthrough in human islet transplantation for treating diabetes mellitus, the limited availability of insulin-producing tissue is still a major obstacle. This has led to a search for alternative sources of transplantable insulin-producing cells including pancreatic duct cells. We aimed to establish in vitro culture of pancreatic duct cells from a partial pancreas tissue in human, which could be harnessed to differentiate into pancreatic beta cells. METHODS: We isolated pancreatic duct cells from small pieces of pancreas tissue (1~3 g) derived from non-diabetic humans (n = 8) undergoing pancreatic surgery due to cancer. Pancreas tissue was finely minced after injection of collagenase P into the parenchyma. The mince was incubated in a shaking water bath at 37degrees C for 25 min and passed through a 150 micrometer mesh. The released cells were recovered, washed, and plated in a dish containing CMRL culture medium with serum. RESULTS: Isolated pancreatic cells grew in monolayer and became confluent in 1~2 wks showing typical epithelial cobblestone morphology. Immunochemistry demonstrated that ~90% of the cultured cells were cytokeratin7-positive duct cells. To induce beta cell differentiation, the cells were incubated in DMEM/F12 culture medium without serum. In addition, treatment with Matrigel overlay, exendin-4, cholera toxin or forskolin was done. Though beta cell differentiation was found by immunostaining and RT-PCR, the differentiation efficiency was very low. Over-expression of neurogenin-3 by recombinant adenovirus did not increase beta cell differentiation of the cultured duct cells significantly. CONCLUSION: We established in vitro culture of pancreatic duct cells from a partial pancreas tissue in human, which differentiate into pancreatic cells. However, a strategy to optimize beta cell differentiation in this model is needed.

Citations

Citations to this article as recorded by  
  • Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
    Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song
    Korean Diabetes Journal.2009; 33(6): 475.     CrossRef
A Case of Hepatic Glycogenosis in a Patient with Uncontrolled Type 1 Diabetes Mellitus.
Seung Hwan Lee, Hyuk Sang Kwon, Jung Ah Shin, Won Chul Kim, Jeong Hoon Kim, Yoon Hee Choi, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2006;30(1):82-86.   Published online January 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.1.82
  • 2,428 View
  • 24 Download
  • 4 Crossref
AbstractAbstract PDF
When a patient with diabetes presents with hepatomegaly and increased level of liver enzymes, glycogenosis or nonalcoholic steatohepatitis (NASH) should be considered. Glycogenosis is mainly developed in patients with type 1 diabetes, when blood glucose level is poorly controlled, when a high dosage of insulin is administered in ketoacidosis, or when glucose is given to control hypoglycemia caused by high dosage of insulin. On the other hand, the main causes of NASH, which are known to mainly affect type 2 diabetes patients, are obesity, dyslipidemia or insulin resistance. Glycogenosis differs from NASH, the former being a reversible change that improves with the control of blood glucose level and the minimum dosage requirement of insulin, and the latter being a progressive disease that may lead to fibrosis or cirrhosis of the liver. However, clinical differentiation of the two diseases is difficult and liver biopsy is helpful for making a definite diagnosis. We present a type 1 diabetes patient with poorly controlled blood glucose level, who have had a frequent history of diabetic ketoacidosis, showing hepatomegaly and a slight increase in liver enzyme level. The patient was diagnosed as diabetic glycogenosis, confirmed by liver biopsy. Strict control of the blood glucose level resulted in rapid improvement showing the reversible nature of the disease.

Citations

Citations to this article as recorded by  
  • Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy
    Yuichi Ikarashi, Tomomi Kogiso, Etsuko Hashimoto, Kuniko Yamamoto, Kazuhisa Kodama, Makiko Taniai, Nobuyuki Torii, Hiroko Takaike, Yasuko Uchigata, Katsutoshi Tokushige
    Hepatology Research.2017;[Epub]     CrossRef
  • Glycogenic hepatopathy in a Korean girl with poorly controlled type 1 diabetes mellitus
    Hwal Rim Jeong, Young Seok Shim, Young Bae Kim, Hae Sang Lee, Jin Soon Hwang
    Annals of Pediatric Endocrinology & Metabolism.2014; 19(1): 49.     CrossRef
  • Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus
    Jae Hwang Cha, Sang Ho Ra, Yu Mi Park, Yong Kwan Ji, Ji Hyun Lee, So Yeon Park, Soon Koo Baik, Sang Ok Kwon, Mee Yon Cho, Moon Young Kim
    Clinical and Molecular Hepatology.2013; 19(4): 421.     CrossRef
  • Hepatic glycogenosis in a patient with poorly controlled type 1 diabetes mellitus
    Hye Young Jin, Dae-Young Kang, Jin-Ho Choi
    Korean Journal of Pediatrics.2009; 52(11): 1279.     CrossRef
Effect of 12-week Oral Treatment with alpha-lipoic acid on the Nerve Conduction in Symptomatic Diabetic Neuropathy.
Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Bong Youn Cha, Ho Young Son, Kwang Woo Lee, Sung Ku Kang
Korean Diabetes J. 2005;29(6):533-539.   Published online November 1, 2005
  • 1,495 View
  • 45 Download
AbstractAbstract PDF
BACKGROUND
Diabetic peripheral neuropathy is multifactorial disorder arising from hyperglycemia and insulin deficiency. It has been suggested that oxidative stress resulting from enhanced free-radical formation and defects in antioxidant defence plays a major role among the putative pathogenic mechanisms of diabetic neuropathy. As alpha-lipoic acid, a natural antioxidant, has been suggested to improve symptoms of diabetic neuropathy, we assessed the efficacy of alpha-lipoic acid on neuropathic symptoms and peripheral nerve conduction in patients with type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: A cohort of 30 type 2 diabetic patients with symptomatic polyneuropathy received a daily dose of 600 mg alpha-lipoic acid, and was followed for 3 months. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) of the feet were scored at monthly interval and summarized as a Total Symptom Score (TSS). Nerve conduction study was done before and after 3 month treatment of alpha-lipoic acid. RESULTS: Treatment of alpha-lipoic acid given 600 mg per oral for 12 weeks improved the symptoms of diabetic polyneuropathy. Effects of alpha-lipoic acid on nerve conduction study were that in the motor nerve, the amplitudes of median nerve and tibial nerve and the conduction velocity of tibial nerve improved after 12 weeks treatment. In the sensory nerve, the conduction velocities of median nerve, ulnar nerve, and sural nerve improved after 12 weeks. CONCLUSION: alpha-Lipoic acid was effective in the treatment of diabetic peripheral polyneuropathy improving both clinical manifestations and nerve conduction. The improvement of clinical manifestations may be due to improved conduction velocity of sensory fibers.
The Relation of Serum Adipokines with Metabolic Risk Factors in Type 2 Diabetic Subjects.
Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Young Mi Ku, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang
Korean Diabetes J. 2004;28(6):521-529.   Published online December 1, 2004
  • 1,144 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
Accumulation of fat, especially in the visceral space, has been claimed to have a causative role in the development of macroangiopathies, because of the secretion of adipokine from the fat tissue. Indeed, the adipocyte secretes chemical messengers (e.g., adipokines) that include leptin, TNF-alpha , IL-6, adiponectin, and resistin. Since adipokines have biologic activities within the vascular system, they might be involved in the development of diabetic angiopathies. The aim of this study is to investigate the relation of adipokine with adiposity, metabolic risk factors, diabetic micro-, and macroangiopathies in type 2 diabetic patients. METHODS: The subjects of this study were 57 type 2 diabetic patients. Anthropometric parameters (height, body weight, waist circumference and body fat composition), cardiovascular risk factors (BP, Lp (a), lipid profile, hs-CRP, fibrinogen), status of glucose metabolism (HbA1c, fasting glucose), diabetic microvascular complication, intima-media thickness (IMT) at both common carotid artery and adipokine (leptin, adiponectin, resistin) were measured. RESULTS: The correlation between the serum adipokine level and duration of diabetes was statistically significant (P <0.01). The leptin was correlated with body mass index (r=0.446, P <0.01), waist circumference (r=0.553, P <0.01) and body fat content (r=0.573, P <0.01). The adiponectin was negatively correlated with plasmatotal cholesterol (r=-0.366, P <0.01) and triglyceride (r=-0.276, P <0.05). The resistin was correlated with Lp (a) (r=0.386, P <0.01), hs-CRP (r=0.413, P <0.01), fibrinogen (r=0.562, P <0.01) and 24hr microalbuminuria (r=0.353, P <0.05). The adiponectin was increased in patients with microalbuminuria than with normo- and macroalbuminuria (P <0.05). The resistin was increased in patients with micro- or macroalbuminuria than normoalbuminuria (P <0.05). The adiponectin was increased in patients with retinopathy (P <0.05). The serum adipokine level was not correlated with IMT of common carotid artery. CONCLUSION: This study reveals that serum adipokine was related with metabolic risk factor in type 2 diabetic patients. Among adipokines, adiponectin and resistin might be involved in diabetic angiopathy. The underlying mechanisms remained to be elucidated in the role of adipokine to the development of diabetic angiopathy.
Effect of Captopril on Insulin Sensitivity for Subjects with Insulin Resistance.
Hye Jung Lee, Hyuk Sang Kwon, Jin Hee Lee, Sung Koo Kang, Yoon Hee Choi, Sung Ha Hwang, Seung Hyun Ko, Jung Min Lee, Kun Ho Yoon, Bong Yun Cha, Won Chul Lee, Kwang Woo Lee, Ho Young Son
Korean Diabetes J. 2004;28(5):416-424.   Published online October 1, 2004
  • 1,316 View
  • 25 Download
AbstractAbstract PDF
BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors are becoming increasingly popular as the first-choice antihypertensive agents for diabetic patients. This could be partly related to their suggested beneficial effects on insulin sensitivity. This study was designed to compare the effect of captopril with that of control (nitrendipine) on insulin sensitivity for subjects with insulin resistance. METHODS: 24 subjects, aged less than 60 years, with their insulin resistance being defined as the area under the curve (AUCi) of insulin that was 2 standard deviations (SD) more than that of the control subjects during oral glucose tolerance test were recruited. A randomized, double-blind, crossover trial was conducted for an 8 weeks treatment period with captopril and the control (nitrendipine) that was given after an initial 6 weeks run-in period. Anthropometric measurement including weight, height, waist and hip circumference, blood pressure (systolic & diastolic), lipid profile blood chemistry, electrolytes levels & renal function testing, and frequently sampled intravenous glucose tolerance tests (FSIGT) for the insulin sensitivity index (SI) & acute insulin response to glucose (AIRg) were also done before and after treatment, respectively. RESULTS: 18 subjects (6 males, 12 females) completed the study. The mean age of the study subjects was 47.9+/-2.9 years (mean+/-SEM), and their BMI was 28.0+/-0.7 kg/m2 (mean+/-SEM).There was a significant decrease in weight (baseline; 71.5+/-9.2 kg vs. captopril; 70.7+/-9.0 kg and nitrendipine; 709+/-9.2 kg, p<0.05, respectively) and BMI (baseline; 28.0+/-3.0 kg/m2 vs. captopril; 27.7+/-2.8 kg/m2 and nitrendipine; 27.8+/-2.9 kg/m2, p<0.05, respectively) for both groups compared with the baseline, but there are no significant differences between the two groups. Triglyceride was significantly decreased after treatment with captopril compared to the baseline and nitrendipine (187.0+/-99.5 mg/dL vs. 224.5+/-134.2 mg/dL, respectively, p<0.05). The SI was significantly increased after captopril treatment compared with the baseline (1.4+/-1.0 vs. 2.5+/-0.8 min-1 per mU/ml, respectively, p<0.05), and the captopril group was significantly higher than that of nitrendipine (1.5+/-1.0 min-1 per mU/ml, p <0.05). Acute insulin response to glucose in both groups was also increased after treatment, but there was no statistically significance. CONCLUSION: Captopril therapy improved insulin sensitivity, and it decreased the concentration of fasting insulin in subjects with insulin resistance.
Relative Hyperglucagonemia and Its Related Factors in Patients with Type 2 Diabetes.
Kang Hyun Choi, Ki Ho Song, Sang Hoon Lee, Seong Hoon Chung, Eun Jung Kim, Seung Hyun Ko, Hyuk Sang Kwon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2004;28(4):338-345.   Published online August 1, 2004
  • 1,406 View
  • 21 Download
AbstractAbstract PDF
BACKGROUND
Excessive secretion of glucagon contributes to metabolic disturbance in type 2 diabetes. A hyperglucagonemic state is likely to be involved in increased hepatic glucose output resulting from both gluconeogenesis and glycogenolysis. The mechanism of hyperglucagonemia, though still unclear, is explained, in part, by the decreased sensitivity of cells to insulin or glucose and disturbances of the normal oscillatory secretory pattern of insulin. The aim of the study was to determine the extent of glucagon excess and its related factors in Korean patients with type 2 diabetes. METHODS: The subjects of this study were 21 controls and 102 type 2 diabetic patients. The blood glucose, glucagon and insulin concentrations were measured at 0, 30, 60, 90 and 120 min after ingestion of 75 g of glucose, and the areas under the curve (AUC) calculated. RESULTS: The AUC of plasma glucose (AUCgc) was significantly higher in the type 2 diabetic patients than in the controls (2,026.1585.8 vs. 854.8190.3 mmol/min, P<0.01), but there was no difference in the AUC of plasma glucagon (AUCgn) between the two groups. The AUCgn in the type 2 diabetic patients was positively correlated with the duration of diabetes (r=0.202, P<0.05) or HbA1c (r=0.208, P<0.05). The AUC of serum insulin (AUCin) was negatively correlated with the duration of diabetes (r=-0.291, P<001). AUCgn, AUCgc and HbA1c in long-term diabetic patients (duration of diabetes 10 years, n=32) were significantly higher compared with recently diagnosed patients (duration of diabetes <1 year, n=38) (11,362.35,981.9 vs. 9,097. 22,990.4 ng/min; 2,119.9519.0 vs. 1,832.2477.6 mmol/min; 9.52.0 vs. 8.32.1%, P<0.05). In addition, the AUCin and insulinogenic index in long-term patients were significantly lower compared with recently diagnosed patients. (Eds note: the highlighted figures are confusing, due to your various uses of commas and period marks, olease clarify?) CONCLUSIONS: Our results suggest that duration of diabetes and poor glycemic control might be closely associated with relative hyperglucagonemia in Korean type 2 diabetic paticnts.
Development of Adult Porcine Islet Isolation Method for Xenotransplantation.
Sung Rae Kim, Kun Ho Yoon, Hyuk Sang Kwon, Sun Hee Suh, Seung Hyun Ko, Jung Min Lee, Soon Jib Yoo, Yoo Bae Ahn, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2004;28(2):75-87.   Published online April 1, 2004
  • 1,223 View
  • 27 Download
AbstractAbstract PDF
BACKGROUND
AND PURPOSE: Xenotransplantation using porcine islet cells might be an alternative to allotransplantation, which has been limited due to the lack of donors. Various researches using porcine islet cells have been performed in foreign countries; however, they have never been studies in Korea. Therefore, the purpose of this study was to explore the possibility of thise new treatment for cases of diabetes by establishing of improved islet isolation skill. METHODS: The pancreas and islets were extracted from pigs weighing around 100kg. To establish an islet isolation method, the islet yield, purity and the distribution size of the isolated islets were step wise compared in various ways, and then the superior method adopted. To determine the conveyance method after organ extraction, the conveyance method of pouring collagenase P was compared with the conveyance method of injecting Custidol. For digestion, the mechanical shaking and static incubation methods were also compared. To isolate islets from the digested pancreata, isolation methods were analyzed using 3 and 4 layers' Ficoll. The islet yield was appraised after their isolation using the optimized islet isolation method. To assess the results of the islet isolation, appraised the purity and the survival rates of cells, the insulin secretion resulting from the glucose stimulation test was examined. RESULTS: The method of injecting 4degrees C Custidol was effective for the conveyance and storage of the isolated pancreas in comparison with an injection of collagenase P(3465+/-1488 IEQ/g pancreas vs. 48+/-1.7 IEQ/g pancreas, p<0.01). The digestion method was superior to the mechanical shaking method at keeping a stable condition(3465+/-1488 IEQ/g pancreas vs. 1265+/-141.4 IEQ/g pancreas, p<0.01). Ficoll isolation using 3 layers gave the same results as using 4 layers. The average weights of the isolate Pancreatic islets was 23.8+/-3.3g. The numbers of islets per gram was 3465+/-1488.2(IEQ), with a the purity of 86.3+/-2.0%, and a survival rate of over 95%. The insulin secretion caused by glucose stimulation substantially increased in concentration from 24 to 72 hours(24hr: 5mM 3.12mU/mL --< 20mM 6.79mU/mL(2.17 fold), 72hr: 5mM 2.38mU/mL --< 9.93mU/mL(4.17fold))
The Effects of High Glucose, Insulin and TGF-beta 1 on Proliferation and Differentiation of the Pancreatic Stellate Cells.
Oak Kee Hong, Hyuk Sang Kwon, Kyu Hyun Yeom, Marie Lee, Ji Hun Yang, Seung Hyeon Ko, Soon Jib Yoo, Hyun Sik Son, Kun Ho Yoon, Bong Yeon Cha, Kwang Woo Lee, Ho Yong Son, Sung Koo Kang
Korean Diabetes J. 2003;27(3):228-240.   Published online June 1, 2003
  • 1,027 View
  • 29 Download
AbstractAbstract PDF
BACKGROUND
Although chronic pancreatitis gives rise to fibrosis of pancreatic exocrine tissue, and type 2 diabetes is accompanied by pancreatic fibrosis, the mechanisms of fibrogenesis in the pancreas have been insufficiently studied. The activated Pancreatic stellate cells (PSC) have recently been identified in human and experimental fibrotic areas from chronic panceatitis tissues. As PSC are similar in their morphology and biochemistry to hepatic stellate cells, they are suspected to play the same role in pancreatic fibrogenesis as the hepatic stellate cells in liver fibrosis. The PSC were isolated from the rat pancreata, and mediators stimulating the proliferation and differentiation identified. METHODS: The pancreatic stellate shaped cells were isolated by a minor modification to the method described by Apte et al (ref), using a Nycodenz gradient. The isolated PSCs were confirmed by phase-contrast and by the immunofluorescence of vimentin, desmin and smooth muscle a-actin (a-SMA). The level of alpha-SMA was quantified by Western blot in the PSCs in the culture, over time, and the cell proliferation was measured by 3[H]-Thymidine incorporation. The effect of the proliferation and differentiation of the PSC were assessed in relation to D-glucose (500 mg/dL), Insulin (10 IU/mL) and TGF-beta (10 ng/mL) treatment of the culture medium. RESULTS: The stellate shaped cells from the rat pancreata grew readily in the culture. Unactivated PSCs, cultured for 3 days, had an angular appearance, contained lipid droplets, manifesting positive vitamin A autofliuorescence, and stained positively for vimentin and desmin, but negatively for alpha-SMA. Within 4~8 days of primary culturing, the PSCs were activated, the sizes and numbers of the fat droplets decreased, the cells flattened, developed long cytoplasmic extensions and expressed alpha-SMA. After 3 passages, almost 100% of the cells were positive for alpha-SMA expression, indicating a myofibroblast type of differentiation in vitro. The addition of high-glucose concentrations and insulin to the activated PSCs significantly stimulated cell proliferation (194.4+/-8.3, 175.0+/-31.0 vs. control), and when the combination of high- glucose and insulin was applied, the cell proliferation was increased to an even greater extent (247.0+/-21.8 vs. control). CONCLUSIONS: Pancreata stellate cells can be isolated, and cultured in vitro, from normal SD rats. High concentrations of glucose and insulin in culture medium activated the PSC proliferation.
The Effect of Nitric Oxide on Insulin Binding and Insulin Receptor Recycling in Bovine Aortic Endothelial Cells.
Hyuk Sang Kwon, Oak Kee Hong, Hee Soo Kim, Jung Min Lee, Sung Rae Kim, Sung Dae Moon, Sang Ah Jang, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2003;27(3):213-227.   Published online June 1, 2003
  • 1,116 View
  • 28 Download
AbstractAbstract PDF
BACKGROUND
The coexistence of insulin resistance and endothelial dysfunction is commonly observed in a variety of metabolic and cardiovascular disorders, including athero-sclerosis and type 2 diabetes mellitus. Because nitric oxide (NO), or nitric oxide synthase (NOS), has been suggested as a significant contributing factor in the development of endothelial dysfunction and insulin resistance, reactive NO or NOS were investigated to see if they contribute to the insulin internalization pathway. METHODS: The production of NO (Nitrite), the expression of eNOS (endothelial NOS), insulin binding and the insulin receptor internalization and recycling, following 48 hours of incubation with bradykinin (BK), acetylcholine (Ach), NG-monomethyl- L-arginine (L-NMMA) and N-nitro-L-arginine methylester (L-NAME) in Bovine aortic endothelial cells (BAECs), were examined. RESULTS: The results were as follows: 1. In relation to the time course, the production of eNOS was increased, but was decreased after 8 hours of incubation. The production of eNOS in the L-NMMA and L-NAME treated groups was significantly decreased compared with that of the controls (p<0.05). 2. The specific insulin bindings to the receptors of the endothelial cells were maximized within 20 mins, and then decreased. At 20 mins, the binding rate of the L-NMMA treated group was significantly decreased compared to that of the controls. At a concentration of 0.4ng/ml of unlabelled insulin, the specific insulin binding of the L-NMMA treated group was significantly decreased compared to that of the controls (p<0.05). 3. The internalization of 125I-insulin into the endothelial cells, as assessed by the acid washing dissociation method, occurred rapidly. The internalized radioactivity of 125I-insulin, at 20 mins, was significantly increased in the BK and Ach groups compared with the controls (p<0.05). 4. The recycling of the internalized insulin receptors showed no significant differences between the study groups, but the recycling was slightly delayed compared with controls in the Ach group. CONCLUSION: In conclusion, the NO generating substances, BK and Ach, and the inhibitory substance, L-NMMA, may influence the binding and internalization of insulin-insulin receptors. Our results suggest that NO might contribute to the transcytosis of insulin in BAECs
Effect of Gi-proteins on Insulin Binding, Internalization and Recycling of Insulin Receptor in Bovine Aorta Endothelial Cell.
Hyuk Ho Kwon, Hyun Shik Son, Jung Min Lee, Seung Hyun Ko, Ok Ki Hong, Sung Dae Moon, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2003;27(1):26-38.   Published online February 1, 2003
  • 1,151 View
  • 18 Download
AbstractAbstract PDF
BACKGROUND
Guanine nucleotide binding proteins (G-proteins) play important roles in the hormonal actions of many signal transduction systems. Possible roles for the Gi-protein in insulin action have been suggested. It is reported that Gi-protein is associated with insulin actions to a greater extent than Gs-protein. There are at least three different subtypes of Gi-proteins (Gi(alpha1), Gi(alpha2), and Gi(alpha3)), however, it is not certain which subtypes are associated with insulin receptors and their action. METHODS: To investigate the effects of Gi-proteins on insulin action, the Gi-proteins were overexpressed in cultured bovine aortic endothelial cells (BAEC), using the DNA-polylysine-adenovirus complex transfection method. After incubating for 24 hours, the BAEC were treated with 200 ng/mL insulin to evaluate the insulin binding, receptor internalization and recycling. RESULTS: The following results were found : 1) The binding of specific insulin bindings to the insulin receptors of endothelial cells were time-dependent, reaching their maximal levels in all cells after 30 minutes. The maximal specific bindings of the control, Gi(alpha1), Gi(alpha2), and Gi(alpha3) were 0.58+/-0.1, 0.54+/-0.08, 0.54+/-0.1, 0.53+/-0.09%, respectively. 2) The internalization of 125I-insulin, into endothelial cells, was assessed by the acid washing dissociation method, and occurred rapidly. There was a significant difference in the internalized radioactivity of the 125I-insulin in the overexpressed Gi(alpha2) protein group compared to the two groups. 3) The recycling of the insulin receptors in the three types of Gi-protein showed no significant difference between the three group. CONCLUSION: In conclusion, the Gi(alpha2) protein may be associated with internalization of the insulin-insulin receptor complex, and appears to be important in both the action of insulin and the intracellular processing of insulin receptors.
Endogenous Streptococcus pneumoniae Endophthalmitis in Diabetic Patients.
Jung Min Lee, Hyun Shik Son, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2002;26(6):520-524.   Published online December 1, 2002
  • 1,024 View
  • 19 Download
AbstractAbstract PDF
Endogenous bacterial endophthalmitis is a rare disease, but has recently been been on the increase due to the increase of chronicity of disease, especially in immunocompromised hosts, and drug abusers, etc. In spite the aggressive topical and systemic management, endophthalmitis has poor prognosis. Therefore, early its diagnosis and appropriate treatment, mandatory for the improvement of the prognosis. We present a case of endogenous Streptococcus pneumoniae endophthalmitis, associated with bacteremia, but with no symptoms, with the exception of ocular pain, in a poorly controlled diabetic patient.
Effects of Nateglinide on the Control of Mealtime Glucose Excursions in Korean Patients with Type 2 Diabetes.
Hyeon Man Kim, Yoon Seok Chung, Kwan Woo Lee, Dae Jung Kim, Hyun Chul Lee, Dong Rim Kim, Dong Seop Choi, Eun Sook Oh, Moo Il Kang, Kwang Woo Lee, Chul Young Park, In Myung Yang, Jin Woo Kim, Young Seol Kim, Hyong Gi Jung
Korean Diabetes J. 2002;26(5):405-415.   Published online October 1, 2002
  • 1,406 View
  • 25 Download
AbstractAbstract PDF
BACKGROUND
Nateglinide belong to a new family of insulin secretagogues that stimulate the early phase of insulin secretion. This study was designed to evaluate the efficacy and adverse effect of nateglinide in Korean type 2 diabetes patients, whose diabetes were inadequately controlled by medical nutrition therapy, focusing on the changes in mealtime glucose excursion (PBG), fasting blood glucose (FBG), glycated hemoglobin (HbA1c) and plasma insulin. SUBJECTS AND METHODS: This multicentered open-label trial was conducted on 66 Korean patients with type 2 diabetes mellitus. The subjects comprised of 36 males and 30 females, with a mean age, and duration of diabetes of 53.9+/-9.6(34~69) years and 39.5+/-44.0 months, respectively. The inclusion criteria were as follows: 1) FBG and PBG before the trial of 6.7~11.1 mmol/l and above 11.1 mmol/l, respectively, 2) changes of FBG and PBG during the 2-week-diet treatment of less than 1.7 mmol/l. PBG, FGB, HbA1c and plasma insulin levels were measured at weeks -2, 0, 2, 4, 8 and 12. Any adverse effects were noted during the study. The data were analyzed by the intent-to treat (ITT) and the per protocol (PP) methods. RESULTS: Nineteen cases were excluded due to protocol violation or withdrawal. The PBG level was significantly decreased during the study 13.7 2.6 mmol/l, before the trail to 9.6 2.8 mmol/l after (p=0.001) which was particularly marked during the first 2 weeks. The FBG, HbA1c and fasting plasma insulin levels were also significantly decreased, from 9.0+/-1.2 to 8.2+/-2.0 mmol/l, p=0.0063), from 8.0+/-1.3% to 7.0+/-1.1% (p=0.0001) and from 9.8 7.2 to 8.0 5.5 pmol/l (p<0.05), respectively. Three adverse events suggested the nateglinide-related diabetes was not serious. CONCLUSION: This study revealed that nateglinide could be used as an effective glucose-lowering agent, especially for the control of mealtime glucose excursion in Korean type 2 diabetes patients who were inadequately controlled by diet alone.
3-Dimensional Long Term Culture of Monolayer Cultured Dispersed Neonatal Porcine Pancreas Cells (NPCC).
Sun Hee Suh, Kun Ho Yoon, Hyuk Sang Kwon, Ok Ki Hong, Jung Min Lee, Ki Ho Song, Soon Jib Yoo, Hyun Sik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2002;26(5):383-395.   Published online October 1, 2002
  • 1,149 View
  • 22 Download
AbstractAbstract PDF
BACKGROUND
We have reported porcine neonatal pancreas cell clusters (NPCCs) to be useful clinical alternative due to their growth potential and convenience. However, to apply the porcine NPCCs in human islet transplantation, there is a need to achieve in vitro maturation of porcine pancreas duct cells for the immediate cure of diabetes, and to escape hyperacute rejection. We have established a long-term 3D culture system of porcine pancreas duct cells for their in vitro induction in differentiated beta-cells. METHOD: For making NPCCs, pancreata from 1~3 days old pigs were minced, digested and cultured for 8 days. After 8 days, the cells were layered with Matrigel. After 50 days, the 3 dimensional cultures, the components of the reconstructed cell clusters were confirmed by three approaches: immunofluorescent staining, mea-surement of glucose stimulated insulin secretion and semiquantitative RT-PCR. RESULT: The monolayers of epithelial cells formed three-dimensional structures of cysts from which 50~200 micro meter diameter islet-like clusters of pancreas cells budded. The insulin and DNA contents, and the ratio of insulin/DNA, did not change significantly, even after 50 days of culturinge. The levels of insulin and galactosyl transferase mRNA showed a tendency to increase in the monolayer culture of the duct cells until day 8, after which the levels significantly decreased. However, the level of glucagon mRNA was maintained until day 50. Compared with their basal secretion at 5mM glucose, the cysts/cultivated porcine islet buds exposed to stimulatory 20mM glucose did not show difference in insulin secretion. CONCLUSION: We have shown the expansion of dispersed porcine neonatal pancreas cells in vitro, and the reconstruction of a three-dimensional structure, following Matrigel overlaying, but were unable to observe the transition of duct cells to beta cells, as observed in human duct cells. Further studies will be required to elucidate this difference.
The Role of Akt-1/PKBalpha on Insulin Action in 3T3-L1 Adipocyte.
Jung Min Lee, Hyun Shik Son, Hyuk Sang Kwon, Seung Ki Kwack, Seung Hyun Ko, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Prem Sharma
Korean Diabetes J. 2002;26(4):274-285.   Published online August 1, 2002
  • 1,207 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
S: Akt/PKB as a serine/threonine kinase is stimulated by insulin and other growth factors. And insulin stimulates glucose uptake by promoting the translocation of glucose transporter 4 (GLUT4) to the cell membrane. But, it is not clear that Akt/PKB, a downstream target of PI 3-kinase, is involved in glucose uptake pathway. In this study, we investigated the role of Akt/PKB, especially Akt-1, on insulin action in 3T3-L1 adipocyte. METHODS: We made recombinant Ad5.Akt-1 vector by the insertion of Akt-1 gene to adenoviral vector. And then, we overexpressed Akt-1 proteins(wild type and kinase inactive type) in 3T3-L1 adipocytes by using a adenoviral transfection method. We observed the changes of glucose uptake, glycogen synthesis, activities of mitogen-activated protein kinase (MAPK, also called extracellular signal-regulated kinase), p70 ribosomal s6 protein kinase (p70s6k), and glycogen synthase kinase 3 (GSK3) according to Akt-1 activity and insulin treatment. RESULTS: First, overexpression of Akt-1 did not affect to glucose uptake, whether insulin stimulates or not. Second, overexpression of Akt-1 did not affect the phosphorylation of p44/42-MAPK, either. Third, the glycogen synthesis was increased by overexpression of Akt-1. CONCLUSION: Akt-1 activation is necessary for glycogen synthesis, but is not essential for glucose transport in 3T3-L1 adipocytes.
The Effect of Long-term Treatment of Ramipril on Glucose Tolerance and Pancreatic Islets in Type 2 Diabetes Animal Model (OLETF Rats).
Seung Hyun Ko, Kun Ho Yoon, Myung Mi Kim, Yu Bae Ahn, Ki Ho Song, Soon Jib Yoo, Hyun Shik Son, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(6):469-482.   Published online December 1, 2001
  • 1,066 View
  • 30 Download
AbstractAbstract PDF
BACKGROUND
In a Heart Outcomes Prevention Evaluation HOPE study, ramipril, a long- acting angiotensin-converting enzyme (ACE) inhibitor, significantly reduced the death rates the number of myocardial infarctions, strokes, heart failure as well as the risk of complications related to diabetes and of diabetes itself. However, it is known that ACE inhibitors improve glucose tolerance or insulin sensitivity or reduce the incidence of diabetes. METHODS: 24 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 400~450 g were used in this study. 4 groups of rats were examined in parallel for 40 weeks. The OLETF rats were randomized for treatment with an aqueous solution of ramipril ( 5mg/Kg) daily [OL (RMP), n=10)] and with saline [OL(CON), n=10)]. The LETO rats were also randomized in the same was as the OLETF rats (LT (RMP), n=10, LT (CON), n=10). The blood glucose level, body weight, systolic and diastolic blood pressure was assessed every month. At 3 and 6 months, the 24hrs urinary protein concentration was measured, and as insulin tolerance test and oral glucose tolerance test were conducted in all experimental groups. After 6 months, the body weight was matched for 2 months in each corresponding group. Subsequently, a 15% sucrose loading was done for 2 months. After the glucose tolerance test, the pancreas was excised and immunohistochemical staining was conducted for insulin to quantify the beta cell mass by a point-counting method. In addition, the islet morphology was evaluated in the pancreas. RESULTS: Ramipril treatment for a period of 6 months improved the 2hr blood glucose level, the area under the glucose curve in the oral glucose tolerance test, insulin sensitivity in addition to lowering significantly systolic and diastolic blood pressure and 24hrs urinary protein level significantly in OLETF rats. Of note, a lower weight gain was observed in both the ramipril-treated animals at 6 months. After weight matching, the AUCg and 2hr blood glucose level values were similar between the corresponding groups, but a 15% sucrose loading worsened the AUCg value. Histologically, the islets were less disorganized and the extent of fibrosis was lower in the ramipril- treated OLETF rats in the trichrome stain. CONCLUSION: Long-term treatment of ramipril, a long acting angiotensin-converting enzyme inhibitor may be useful for suppressing weight gain and proteinuria in addition to having aprotective effect on the islet to harmful stimuli such as hyperglycemia.
Selective beta-Cell Loss and alpha-Cell Expansion in Islets of Type 2 Diabetic Patients.
Jae Hyoung Cho, In Kyu Lee, Kun Ho Yoon, Seung Hyun Ko, Sun Hee Suh, Jung Min Lee, Sung Rae Kim, Yoo Bae Ahn, Jong Min Lee, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(2):164-177.   Published online April 1, 2001
  • 1,467 View
  • 28 Download
AbstractAbstract PDF
BACKGROUND
It has been reported that a decrease in the beta-cell mass, may play a major role in the development of type 2 diabetes. Some stimuli that cause beta-cell loss can stimulate neogenesis from precursors as well as replication of matured beta-cells. In an animal-based studies reported that alpha-cells can also be produced in the course of alpha-cell neogenesis, after being treated with streptozotocin. Through this research, we attempted to determine the change of beta-cell mass according to the changes in alpha-cell mass and to characterize the size of the beta-cell nucleus observed in type 2 diabetes. METHOD: To estimate the relative fraction of alpha- and beta-cell mass in the pancreas, we counted beta-cells and alpha-cells by point count method. We also performed a double immunohistochemical staining with glucagon and insulin antibodies to calculate the ratio between these two cells area in the pancreas (A/B ratio). In order to measure the size of the beta-cell nucleus, an immunofluorescence staining of the nucleus and insulin was carried out. Data were gathered from type 2 diabetic subjects (n=19) and normal controls (n=8). RESULTS: Although there was no statistical difference, we observed the tendency of decrease of beta-cell mass and increase of alpha-cell mass in the pancreas of type 2 diabetic patients. The ratio of alpha-to beta-cell area in islet (A/B ratio) increased to 0.81+/-0.76 in diabetic patients compared to control with 0.26+/-0.25 (p<0.01). The mean of the A/B ratios of the islets more than 22,000 micro m2 was 1.64+/-1.10, whereas that of the islets less than 22,000 micro m2 was 0.73+/-0.67 in type 2 diabetic patients (p<0.01). The size of the beta-cell nucleus in both diabetic subjects and normal controls was bigger than that of exocrine cells (p<0.05) and 2.9% of beta-cells in type 2 diabetic subjects showed substantially enlarged nuclei more than M+5SD (M and SD means the average and standard deviation of nucleus size of exocrine cells, respectively) whereas this type of nucleus was found in only 0.5% of beta-cells in normal controls (p<0.05). CONCLUSION: The islet pathology in type 2 diabetes could be characterized by an expansion of alpha-cells associated with the selective loss of beta-cells. Some beta-cells found in diabetes showed a significant increase in size of the nucleus. Through the results from this study, we postulate that enlarged beta-cell nucleus and reverse of A/B ratio in the islets could be a marker of early senescence of beta-cells in patients with type 2 diabetes mellitus.
Relationship Between Intimal-Medial Thickness (IMT) of the Carotid Artery and Atherosclerotic Risk Factors in Patients with type 2 Diabets Mellitus.
Yu Bae Ahn, So Lyung Jung, Seung Hyun Ko, Ki Ho Song, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(2):142-151.   Published online April 1, 2001
  • 1,137 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
Diabetes mellitus is a major independent risk factor for atherosclerosis. In recent years non-invasive high resolution B-mode ultrasound methods have been developed to measure the IMT (intima-media thickness) of the carotid artery as an index for early atherosclerosis. The aims of this study were to measure IMT in type 2 diabetic patients, to investigate the relation of various cardiovascular risk factors to IMT, and to evaluate the difference in IMT according to presence of diabetic complication. METHODS: IMT was measured by ultrasound B-mode imaging in 300 subjects with type 2 diabetes mellitus (131 male, 169 female adults aged 53.4+/-9.5 years, duration of diabetes 7.4+/-6.3 years). All subjects underwent coronary artery disease (CAD) risk factors assessment and the presence of diabetic complications were evaluated. RESULT: There were positive correlations between IMT and age, duration of diabetes, LDL-C, systolic blood pressure and Lp (a) level. Multiple linear regression analysis demonstrated that in type 2 diabetic patients, the variables that interact independently with IMT were age, systolic blood pressure, levels of total cholesterol, HDL cholesterol and sex. IMT was significantly increased in type 2 diabetic patients with macrovascular complication regardless of presence of microvascular complication. But there was no significant difference in IMT according to Lp (a) level, presence of microalbuminuria, mode of treatment and glycemic control. CONCLUSION: The Intima-Media thickness of patients with type 2 diabetes mellitus was associated with age, systolic blood pressure, levels of total cholesterol, HDL-C and sex.
Effect of Oxidized LDL on the Amount of Insulin Receptor and Gi-proteins in the Caveolae of Bovine Aortic Endothelial Cells (BAEC).
Sung Yoon Jeon, Hyun Shik Son, Jung Min Lee, Sung Dae Moon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(1):71-82.   Published online February 1, 2001
  • 1,293 View
  • 24 Download
AbstractAbstract PDF
BACKGROUND
AND AIMS: Oxidized LDL (ox-LDL) may induce endothelial cell dysfunction and suggested to have an association with atherosclerosis or insulin resistance. Several studies have shown that ox-LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi-proteins). G-protein coupled receptors (GPCRs) can be internalized via caveolae. Caveolae are small flask-shaped invaginations of the plasma membrane, characterized by high levels of cholesterol and glycosphingolipids and also by the presence of caveolin, a 20-24 kDa integral membrane protein. G-proteins are enriched within caveolae membranes, where caveolin-1 directly interacts with the -subunits of G-proteins. It is reported that functional changes of G-proteins such as mutational or pharmacological activation of G-proteins affect direct interaction between G-proteins and caveolin-1. Thus, we investigated the effect of ox-LDL on the change of the amount of insulin receptor and Gi proteins in the caveolae. MATERIALS AND METHODS: ox-LDL was prepared by exposing samples of native LDL (n-LDL) to CuSO4 for 24 hours. Caveolae were extracted after treating BAECs at several concentrations of ox-LDL (10, 50, 100 g/mL) for various durations (0-48 hr), and we investigated the changes of the amount of caveolin-1, Gi -proteins and insulin receptor using immunoblot. RESULTS: While the amount of caveolin-1 was decreased, the amount of insulin receptor, Gi 2 and Gi 3 proteins in caveolae were also decreased after treatment of ox-LDL on the BAECs (insulin receptor: 66%; Gi 2 protein: 33%; Gi 3 protein: 66%, p<0.05). The amount of caveolin-1 was increased for the first 6 hours and then decreased, however, the amount of Gi -proteins and insulin receptor were vice versa during 48 hours incubation. CONCLUSION: These results indicate that ox-LDL can affect the change of the amount of insulin receptor and Gi-proteins in caveolae and it may induce endothelial cell dysfunction.
Effects of Cilostazol on Insulin Resistance in OLETF Rats.
Sung Rae Kim, Ki Hyun Baek, Seung Hyun Ko, Jung Min Lee, Sang Ah Chang, Yoo Bae Ahn, Soon Jib Yoo, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(1):63-70.   Published online February 1, 2001
  • 1,351 View
  • 21 Download
AbstractAbstract PDF
BACKGROUND
Insulin resistance is one of the major pathophysiology of type 2 diabetes mellitus. It is reported that cilostazol and cyclic AMP phosphodiesterase inhibitor has the anti-platelet effect as well as an improvement of hypertriglyceridemia in addition to vasodilatation. Furthermore, the previous reports indicated that there is a positive relationship between insulin resistance and dyslipidemia. Thus, we investigated the effects of cilostazol on insulin resistance in OLETF rats using the euglycemic hyperinsulinemic glucose clamp technique, and lipid levels. METHODS: Fifteen five months old OLETF rats were fed for 4 weeks(8 treated with cilostazol and 7 were control), and compare to 20 same aged LETO rats (8 treated with cilostazol and 12 were control) through the glucose infusion rate on euglycemic hyperinsulinemic glucose clamp and lipid profiles. RESULTS: The glucose infusion rate was higher in the cilostazol treated OLETF rats than in the non-cilostazol treated OLETF rats (0.021+/-0.0031 vs 0.027+/-0.0036 mL/min). The levels of free fatty acids (2424.8+/-652.7 vs 1061.8+/-223.2 Eq/L), total cholesterol (145.7+/-17.9 vs 115.4+/-7.6 mg/dL) and triglyceride (146.5+/-46.6 vs 76.1+/-12.5 mg/dL) of cilostazol treated OLETF rats were significantly lower than those of non-cilostazol treated OLETF rats. CONCLUSION: This study result suggest that cilostazol may improve the insulin resistance through the improvement of dyslipidemia in OLETF rats.
The Changes of Beta Cell Mass and Islet Morphology in OLETF (Otsuka Long Evans Tokushima Fatty) Rats After Partial Pancreatectomy .
Seung Hyun Ko, Kun Ho Yoon, Sun Hee Suh, Yu Bae Ahn, Soon Jib Yoo, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(1):50-62.   Published online February 1, 2001
  • 1,085 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
Insulin resistance and incomplete beta cell compensation play a major role for development of type 2 diabetes. When insulin resistance were induced by any cause, appropriate beta-cell proliferation is a key factor for maintaining the normal glucose metabolism. Compensatory beta-cell proliferation for adapting to increased insulin resistance might be achieved by neogenesis of beta-cell from duct cells, replication of preexisting beta-cells and also inhibition of beta-cell apoptosis. Previously incomplete beta-cell compensation was observed in OLETF rat, animal model of type 2 diabetes, after partial pancreatectomy, but there were no reports about the underlying pathogenesis. Therefore, this study was designed to study on the mechanism of incomplete beta-cell compensation in OLETF rat after partial pancreatectomy especially focus on beta-cell proliferation. METHODS: 12 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 280-320 g were used. 80% partial pancreatectomy was done. Experimental animals were divided into the 4 subgroups by date of killing after surgery: 0, 3, 90 days. After glucose tolerance test, pancreas remnant was excised and immunohistochemical staining was done for insulin to quantify the beta cell mass by point-counting method and also observed the amount of fibrosis of the islets after Masson's trichrome staining of the pancreas. RESULTS: We observed that impaired glucose tolerance or diabetes were developed after 80% pancreatectomy. We observed rapidly proliferating duct cells in the adjacent area of common pancreatic duct and main duct even up to 90 days after partial pancreatectomy. In OLETF rats, beta cell mass was not increased enough compared to LETO rats and some destructive features of islet architectures were noted at 90 days after pancreatectomy. CONCLUSION: The changes of beta cell mass seems to be a dynamic process adjusting to metabolic demand. Severe hyperglycemia and islet disorganization were apparent in OLETF rats despite of existence of beta cell regeneration and renewal process. So it seemed that hyperglycemia accelerated aging process or senescence of beta cells in OLETF rats.
The Serial Changes of Blood Glucose and Lipid Levels Following Allogeneic Bone Marrow Transplantation and Related Clinical Factors.
Won Young Lee, Moo Il Kang, Eun Sook Oh, Ki Won Oh, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Wan Sik Shin, Woo Sung Min, Choon Choo Kim
Korean Diabetes J. 2000;24(6):689-698.   Published online January 1, 2001
  • 1,130 View
  • 21 Download
AbstractAbstract PDF
BACKGROUND
In bone marrow transplantation (BMT), recipients are usually younger and immunosuppressants are open used in shorter period than in solid organ transplantation. Therefore, there might be a difference in glucose and lipid metabolism between BMT and solid organ transplantation. However, the serial changes of metabolic parameters following BMT have not been studied. There fore, the aim of this study is to investigate the serial changes of blood glucose, lipids and the putative factors that are related with these changes after BMT. METHODS: We have prospectively investigated 43 patients who underwent allogeneic BMT . Fasting plasma glucose (FPG), total cholesterol, triglyceride and high-density lipoprotein (HDL) were measured before BMT, and at 1, 2, 3, 4, 12 weeks and 6 months after BMT. The serial changes of these metabolic parameters according to clinical factors including type of BMT, mean daily steroid dosage, and occurrence of graft versus host disease (GVHD) were examined. RESULTS: 1. Mean FPG level increased during 4 weeks after BMT and remained above basal value at post-transplant 6 months. Total Cholesterol level was increased during initial 4 weeks after BMT and was above basal value at post-BMT of 3 and 6 months. Triglyceride level was progressively increased during initial 4 weeks after BMT, but returned to basal value thereafter. HDL-cholesterol level was significantly decreased during initial 4 weeks after BMT, but returned to basal value thereafter. 2. Patients with FPG above 126 mg/dL at post-transplant 6 months were 7 out of 43 patients (16%). Comparing patients with FPG above 126 mg/dL and the other patients, the former received larger amounts of daily steroid and had lower HDL-cholesterol level. 3. The changes of metabolic parameters were different according to type of BMT, steroid dose, and occurrence of GVHD. CONCLUSION: Although there was increase of FPG, TC, TG and decrease of HDL-C during initial 4 weeks after BMT, these metabolic changes recovered slowly thereafter. Immunosuppressants are thought to be associated with these changes. Further observation will be needed for the long-term effect of BMT on metabolic changes.
Changes in the Amount and Function of Gi Protein in the Liver Cells of Streptozotocin-Induced Diabetic Rats.
Sun Myeong Ock, Hyun Shik Son, Oak Kee Hong, Jung Min Lee, Sung Rae Kim, Sang Ah Chang, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2000;24(6):666-677.   Published online January 1, 2001
  • 1,209 View
  • 21 Download
AbstractAbstract PDF
BACKGROUND
The functional and expressional changes of Gi proteins in diabetes have been investigated extensively, no agreement has been reached in the results. Moreover, studies using rats with different diabetic duration, and using subunits (Gialpha) of Gi proteins are lacking in literatures. Thus, we assessed the changes according to the duration of diabetes and examined the expressional changes of Gialphaand functional changes of Gi proteins in hepatocytes from streptozotocin-induced diabetic rats. METHODS: Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes ; 1, 2, 3 and 5 weeks after the onset of diabetes, livers from the control and diabetic rats were fractionated into homogenate, interface, and plasma membrane. The levels of Gialpha1&2, Gialpha3 were quantified with western blots in each fraction. The functional changes of Gi proteins were evaluated by performing pertussis toxin-catalyzed ADP-ribosylation and measuring GTP S binding activity. RESULTS: 1) Gialpha2 and Gialpha3 were present mainly in the plasma membrane of hepatocytes in the diabetic and control rats, but the levels of these subunits were significantly higher in the diabetic rates than in the control rats (p<0.01). The levels of these subunits were not affected by the duration of diabetes. 2) In streptozotocin-induced diabetic rats, the levels of ADP-ribosylation of Gi proteins in liver plasma membranes decreased when pertussis toxin-catalyzed ADP-ribosylation was performed with liver tissues. However, the levels of these proteins were not affected by the duration of diabetes. 3) For the GTP S binding activity of Gi proteins in liver plasma membranes, the diabetic rats showed significantly less activity than the control rats (p<0.01). However, the activity was not affected by the duration of diabetes. The activity was somewhat restored by the insulin treatment of liver plasma membranes in diabetic rats. CONCLUSION: These results suggest that the insulin-deficient diabetic state induces the quantitative and functional changes in Gi proteins of hepatocytes regardless of the duration of diabetes. Therefore, these changes in Gi proteins may be the important compensatory reactions for the insulin resistance occurring in the insulin deficient state.
The Effect of Increased Beta Cell Mass on Glucose Tolerance in Rat.
Eun Sook Oh, Kun Ho Yoon, Sun Hee Seo, Sook Young Lee, Seung Hyun Ko, Won Young Lee, Sung Rae Kim, Moo Il Kang, Bong Yon Cha, Kwang Woo Lee, Ho Young Son, Sung Goo Kang
Korean Diabetes J. 2000;24(6):629-640.   Published online January 1, 2001
  • 1,199 View
  • 23 Download
AbstractAbstract PDF
BACKGROUND
The aim of the present study is to evaluate the effect of increased beta cell mass by continuous 96-hour 50% glucose infusion on glucose tolerance in insulin resistance state induced by high fat diet in normal Sprague-Dawley rats. METHODS: The adult Sprague-Dawley rats weighing 200-250 gm were infused with 50% glucose or 0.45% saline via external jugular vein catheter for 96 hours. The both groups of rats were then randomly stratified into the two subgroups, and fed either high fat diet (54% of energy from fat) or normal rat chow (8.6% of energy from fat) for 4 weeks. On day 28, blood was collected for measuring the serum concentration of insulin, and oral glucose tolerance test (2 gm/kg body weight) was performed after overnight fasting. The beta cell mass was counted with the morphometric point-counting technique of Weibel. RESULTS: After the 96 hour infusion, the percentage of beta cell mass was significantly increased in glucose-infused rats when compared to the saline-infused group (p=0.03) and maintained up to day 28. Body weight gains were significantly greater in glucose infused rats than those of saline infused group (Increased value of weight : 142.9+/-15.2 g in glucose infused rats vs 125.3+/-21.1 g in saline infused rats, p=0.01). In the saline infusion-high fat diet group, the number of rats with impaired glucose tolerance was higher than those of other group (p<0.005). The glucose values at 90 minute and 120 minute were higher in saline infusion-high fat diet group than in glucose infusion-high fat diet group (p< 0.05). CONCLUSION: Our findings suggest that the increased beta cell mass has a favorable effect on glucose tolerance in insulin resistance state which were evoked by high fat diet.
Quantification of the Pancreatic -cell Mass in Normal and Type 2 Diabetic Subjects in Korea.
Kun Ho Yoon, Seung Hyun Ko, Jung Min Lee, Sung Rae Kim, Sun Hee Seo, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Yong Gui Kim, In Sung Moon, Myung Deuk Lee, Dong Ku Kim, Kyo Young Lee, Chan Suk Kang, Byung Ki Kim
Korean Diabetes J. 2000;24(5):524-532.   Published online January 1, 2001
  • 1,495 View
  • 18 Download
AbstractAbstract
BACKGROUND
There have been several reports about insulin secretory impairment in non-obese type 2 diabetic patients and even in impaired glucose tolerant subjects in Korea. Insulin secretory impairment might be induced by insufficient beta-cell mass, functional defects of beta-cells or both. To clarify the cause of impaired insulin secretion in type 2 non-obese diabetic patients in Korea, beta- cell masses were quantified in normal and type 2 diabetic subjects. METHOD: Normal pancreases were procured by 6 heart-beating non-diabetic donors under informed consent from relatives and approval of the university ethical committee. To quantify the beta cell mass and insulin content in various part of the pancreas, first we divided it into 3 parts: head, body and tail, and then each three parts were weighed and subdivided again into 8 segments equally. For diabetic patients, tissue sections were obtained from 15 partial or total pancreatectomized type 2 diabetic patients of any causes. After being fixed, tissues were immunostained using the Streptavidin-biotin-peroxidase method with anti-insulin antibody. Beta cells were counted by point count method. RESULTS: The mean value of total pancreas weight of normal subjects (n=6) was 77.1+/-14.6 g, that of mean relative volume of beta cells in the pancreas was 2.1+/- 0.9%, ranging from 1.4% to 3.1% (head 2.3+/-0.6%, body 1.8+/-0.2%, tail 2.2+/-0.4%). Mean value of total beta cell mass which was calculated from relative volume of beta-cells and weight of each portions was 1.3+/-0.3 g, ranging from 1.2 g to 1.9 g (head 0.6+/-0.3 g, body 0.4+/-0.2 g, tail 0.4+/-0.2 g). Mean insulin content per pancreas was 63.6+/-46.6 g, ranging from 27.8 to 137.2 g/pancreas (head 25.1+/- 19.1 g, body 20.8+/-15.5 g, tail 17.7+/-14.9 g). In diabetic patients, relative volume of beta cells in tissues were variable from 0.4% to 2.8% and there was good correlation between beta-cell mass and body mass index of the diabetic patients. However we can't find the correlation among relative volume of beta-cell, (r2=0.55, p<0.05) duration of diabetes and age. Remarkable heterogeneity for loss of beta-cells in the islets of diabetic patients was observed even in the same lobe of pancreas. There were no evidence of lymphocytic infiltration in the islets. CONCLUSION: Insufficient beta cell mass seems to be a main cause for insulin secretory impairment in non-obese type 2 diabetic patients in Korea.
Effect of Overexpression of Gi Proteins on Insulin Actions in 3T3-L1 Adipocytes.
Hyun Shik Son, Bong Yun Cha, Sung Dae Moon, Jung Min Lee, Ok Ki Hong, Sang Ah Chang, Yu Bae Ahn, Kun Ho Yoon, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2000;24(4):404-412.   Published online January 1, 2001
  • 1,172 View
  • 18 Download
AbstractAbstract PDF
BACKGROUND
It has been reported that G proteins are involved in biological actions of insulin. Especially, Gi protein is more associated with insulin actions than Gs proteins. Gi protein has at least three different subtypes of Gi 1, Gi 2 and Gi 3 protein. However, it is not certain which subtypes of Gi proteins are associated with biological actions of insulin. METHODS: To investigate which subtypes of Gi proteins are associated with insulin action, we overexpressed three different kinds of Gi protein, Gi 1, Gi 2 and Gi 3 protein, in 3T3-L1 adipocytes using DNA-polylysine-adenovirus complex transfection method. After incubating for 2 hours, 3T3-L1 adipocytes were treated with 100 nM insulin for the evaluation of biological actions of insulin. Moreover, to elucidate insulin stimulated insulin receptor autophosphorylation and IRS-1 phosphorylation, 3T3-L1 adipocytes were stimulated with 100 nM insulin for 10 minutes, homogenized and immunoprecipitated with anti-phosphotyrosine antibody. RESULTS: Transfection with Gi 2 gene resulted in increment in insulin-stimulated [3H]2-deoxyglucose (DOG) uptake without affecting basal 2-DOG uptake, but not with Gi 1 and Gi 3 gene transfection. There was unchanged glycogen synthesis rate in all three Gialphasubtypes. Insulin-induced increments of insulin receptor autophos phorylation and IRS-1 phosphorylation were found in Gi 2 protein overexpressed group, only. CONCLUSION: These results suggest that Gi 2 protein may be associated with regulation of biological actions of insulin.
In Vitro Expansion and Differentiation of Islet Precursor Cells from Cultured Neonatal Porcine Pancreatic Tissue.
Yu Bae Ahn, Kun Ho Yoon, Sun Hee Seo, Seung Hyun Ko, Ki Ho Song, Je Ho Han, Soon Jip Yoo, Hyun Sik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2000;24(3):310-322.   Published online January 1, 2001
  • 1,064 View
  • 19 Download
AbstractAbstract PDF
BACKGROUND
Neonatal porcine pancreas is an attractive alternative source for islet transplantation because of its growth potential and availability. Porcine neonatal pancreatic cell clusters (NPCCs) consist mainly of protodifferentiated cells expressing both the duct cell marker pancytokeratin and islet hormones. In this study, we investigated to expand and mature the pancreas duct cells contained in porcine NPCCs with extracellular matrix. METHODS: For NPCCs, pancreas obtained from neonatal pigs were minced, digested with collagenase and cultured overnight. Then NPCCs were further dispersed to small cell groups and cultured on HTB-9 extracellular matrix: the tissue attached and formed monolayer patches. At the 3rd and 8th days, tissue was fixed, immunostained for pancytokeratin (panCK), vimentin (VT) and islet hormones. RESULTS: During 5 days culture, the total cell numbers increased 3.2 fold on the matrix, and 1.6 fold on the sticky dish, respectively. Insulin positive cells (Ins+) were 6.0% of total cells at day 3 and increased 1.6 fold in numbers at day 8. There was significant increase in DNA content of NPCCs in monolayers on both sticky dishes and HTB-9 matrix. In contrast, insulin content of both groups decreased during culture periods. Until 8 days of culture after dispersion of porcine NPCC, most duct cells costained with panCK and VT. CONCLUSION: We observed NPCCs were composed of many of duct cells which were known to be endocrine precursor cells and monolayer culture of NPCC withextracellular matrix resulted in the proliferation and differentiation of pancreatic duct cells.
Risk Factors of Posttransplant Diabetes Mellitus after Allogeneic Bone Marrow Transplantation.
Ki Won Oh, Won Young Lee, Moo Il Kang, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Wan Sik Shin, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Woo Sung Min, Choon Choo Kim
Korean Diabetes J. 2000;24(2):225-234.   Published online January 1, 2001
  • 1,164 View
  • 19 Download
AbstractAbstract PDF
BACKGROUND
Although increasing number of patients are survived after organ transplantation, morbidity and mortality due to cardiovascular disease is thought to be the key risk factor for the long-term tranplant survivors. Many studies have shown that posttransplant diabetes mellitus, dyslipidemia, and hypsrtension are major causes of accerelated atherosclerosis after organ transplantation. Immunosuppressants, rejection, family history of DM, certain HLA phenotypes, pretransplant age and fasting glucose concentration are suggested as etiopathogenic factors of posttransplant diabetes mellitus (PTDM) after solid organ transplantation, while the risk factors of PTDM after bone marrow transplantation (BMT) is unknown. The aim of our study to investigate the clinical characteristics and possible risk factors for PTDM after BMT. METHODS: Age, male to female ratio, body mass index, mean daily steroid dosage, mean daily cyclosporin dosage, incidence of graft versus host disease(GVHD), incidence of cytomegalovirus (CMV) disease, fasting plasma glucose concentra-tion, serum lipid profiles, and HLA phenotypes were retrospectively examined in 15 PTDM patients and 68 non-diabetic patients after allogeneic BMT. RESULTS: 1. Among 490 allogeneic BMT, PTDM developed in 15 patiants (3.1%). The mean duration from BMT to onset of PTDM was 26,6+/-33,9 days. 2. When compared between the PTDM and non-diabetic patients, mean daily steroid dosage, incidence of GVHD, and incidence of CMV disease were significantly different. 3, HLA phenotypes, HLA-DR52 and DR53, were more frequently observed only in PTDM patients. 4. At the onset of PTDM, we observed that fasting plasma glucose, total cholesterol, and LDL-cholesterol concentration were significantly elevated in pre-BMT state. CONCLUSION: We conclude that posttransplant diabetes mellitus after BMT, frequently develops in patients with a predisposition of high-dose steroid, GVHD, HLA-DR52 and DR53 phenotypes. This study suggested that high-dose steroid therapy, mainly due to GVHD, might be the critical factor in the onset of PTDM after allogeneic BMT and that the risk may be affected by HLA-DR52 and DR53 phenotypes.
The Changes of Expression of Intermediate Flament in Pancreatic Duct Cells During Proliferation and Differentiation after 90% Pancreatectomy in Rats.
Seung Hyeon Ko, Kun Ho Yoon, Sun Hee Seo, Jung Min Lee, Ki Won Oh, Sang Ah Chang, Hye Soo Kim, Yoo Bae Ahn, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2000;24(2):191-201.   Published online January 1, 2001
  • 1,169 View
  • 21 Download
AbstractAbstract PDF
BACKGROUND
Neogenesis of the beta calls from ductal cells is the main mechanism of the increased beta cell mass after partial pancreatectomy. For the transdifferentiation from the duct cells to the beta cells, de-differentiation of the duct cells is needed because duct cells are also terminally differentiated cells already. But there was no clear evidence of de-differentiation of the duct cells during duct call proliferation so far. Herein we report the changes of intermediate filament protein expression in rapidly proliferating duct cells after partial pancreatectomy for the evidence of de-differentiation of the duct cells. METHODS: 45 week-old Sprague-Dawley rats weighing 80~120 g were used. 90% partial pancreatectomy was done. Experimental animals were divided into 5 subgroups by date of killing after surgery: 1, 3, 7, 14, 30 days, Pancreas remnant was excised and immunohistochemical stain was done for pancytokeratin (Pan-CK) as a epithelial cell marker and vimentin (VT) as a mesenchymal cell marker. We observed the double stained slide with pan-CK and VT antibody using confocal microscope for costaining analysis over time. The sections were also immunostained with anti-insulin antibody for the quantification of the beta cell mass by point-counting methods. RESULTS: We observed impaired glucose tolerance and diabetes were developed affer 90% pancreatectomy. Significant increase of the weight of pancreatic remnant, beta cell and duct cell mass were observed about 14 days after pancreatectomy. We observed the co-expression of VT and pan-CK intermediate filament protein in rapidly proliferating duct cells in the area of common pancreatic duct and main duct at one day after partial pancreatectomy. 3 days affer partial pancreatectomy, VT and pan-CK costained duct cells were mainly observed in the rageneration focus of the duct cell proliferation. 30 days after partial pancreatectomy, we could not find any costaining duct calls in the remnant pancreas. CONCLUSION: The vimentin intermediate filament, a marker of mesenchymal cell was expressed in proliferating ductal cells after pancreatectomy. We could suspect that pancytokeratin and vimentin co-expression is a good marker for de-differentiation of proliferating duct cells.
Methylenetetrahydrofolate Reductase Polymorphism in Korean Type 2 Diabetic Patients with Macroangiopathy.
Ki Won Oh, Won Young Lee, Yoo Bae Ahn, Ki Ho Song, Soon Jib Yoo, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 1999;23(5):625-634.   Published online January 1, 2001
  • 1,000 View
  • 18 Download
AbstractAbstract PDF
BACKGROUND
Hyperhomocysteinemia is an inde-pendent risk factor for cardiovascular disease. Recently, a mutation (677CT) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene, leading to the substitution of valine (V) for alanine (A). This mutation causes a reduced folate-dependent enzyme activity which leads to increased homocysteine. In this study, we examined the association between the V allele of the methylenetetrahydrofolate reductase gene and macroangiopathy in Korean patients with type 2 diabetes mellitus. METHODS: In 54 type 2 diabetic patients with macroangiopathy and 198 normal subjects, the MTHFR genotypes were analyzed by polymerase chain reaction (PCR), followed by Hinfl digestion. To confirm the detection of the MTHFR polymorphism by the PCR-restriction fragment length polymorphism (RFLP) analysis, DNA Sequencing was performed on the PCR products. RESULT: The allele frequency of the V mutation was slightly higher in the patients than in the normal subjects, but that was statistically not significant. The crude ORs and 95% CIs for the allele frequency of the V mutation were 1.16 (0.76~1.79). Genotype frequencies were 35.9% for AA, 48.4% for AV, and 15.7% for VV in the normal subjects. And they were 31.5% for AA, 50.0 % for AU, and 18.5 % for VV in the patients. The crude ORs and 95% CIs for the VV genotype were 1.22 (0.56~2.67). In multiple regressian model, the VV genotype was not associated with diabetic macroangiopathy. CONCLUSION: Although, the frequencies of VV genotype in Korean normals (=16%) are higher than those of other thical populations (=12%), this mutation is not associated with macroangiopathy in type 2 diabetic patients. But, our sample size was too small and larger cohort studies will be needed to confirm the effect of MTHFR polymorphism on the development of macroangiopathy in diabetic patients.
Effect of Oxidezed LDL in Insulin Binding, Internalization and Recycling of Insulin Receptor in Cultured Bovine Aortic Endothelial Cells.
Sung Dae Moon, Bong Yun Cha, Hye Soo Kim, Sang Ah Jang, Yu Bae An, Ki Ho Song, Je Ho Han, Soon Jib You, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 1999;23(3):243-255.   Published online January 1, 2001
  • 1,085 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
Endothelial dysfunction is perhaps one of the earliest manifestations of atherosclerosis. This abnormality is in part due to altered membrane signal transduction in endothelial cells. Oxidized LDL that is atherogenic may induce endothelial dysfunction, and its presence has been documented in atherosclerotic vessels. Many studies have shown that oxidized LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi- protein). It is also known that G-protein is involved in insulin recycling on cultured human umbilical vein endothelial cells. Therefore, to determine the effect of oxidized LDL on endothelial cells: insulin binding, internalization, and the recycling of insulin receptors were assessed in cultured bovine aortic endothelial cells treated with native LDL, oxidized LDL, and in some cells pretreated with pertussis toxin before the incubation with oxidized LDL. METHOD: Native LDL (density 1.019 1.063 g/mL) was obtained from using the rapid single discontinuous density gradient ultracentrifugation of plasma samples from a single donor. Oxidized LDL was prepared by exposing samples of native LDL to CuSO4 (5 uM) at 37't for 24 hours. Endothelial cells at 80% confluence were treated with the indicated concentrations of native LDL, oxidized LDL, and some cells were pretreated with pertussis toxin for 6 hrs before the incubation with oxidized LDL. These cells were incubated for 24 72 hours. RESULTS: 1. Binding of (125)I-insulin(0.17nM) to endothelial cells treated with increasing concentrations of oxidized LDL shows dose-dependent decrease. There were significant differences in insulin binding between native LDL and oxidized LDL-treated cells (p<0.05). Binding of 'I-insulin (0.17 nM) to endothelial cells treated with increasing culture time of oxidized LDL shows more decreased than that of native LDL significantly (p<0.05). And oxidized LDL had additive effect, but not significant, with pertussis toxin on the specific (125)I-insulin binding to bovine aortic endothelial cells. 2. Internalization of insulin receptors reached rapidly to its maximal level around 30min at 37'C. At 60 min, oxidized-LDL treated cells was less increased in internalization of insulin receptors than that of native LDL treated cells [59.1+1.9% of total cell associated insulin (mean+SE) vs. 67.5+1.1%, p<0.05]. There were additive effects, but not significant differences, between oxidized LDL and pretreated with pertussis toxin before the incubation with oxidized LDL. 3. After 30 min of incubation with unlabeled insulin (33 nM), insulin binding in oxidized LDL treated cells was significantly higher compared to native LDL treated cells (69.0+2.5% of control values vs. 63.7+1.2%, p<0.05), suggesting that oxidized-LDL decreased internalization of insulin receptors. And during the process of recycling, there were significant differences in insulin receptor recycling between the oxidized LDL and native LDL treated cells, but oxidized LDL had an additive effect, but not significant, with pertussis toxin on insulin receptor recycling to the bovine aortic endothelial cells. CONCLUSION: 1. The findings in this study suggest that oxidized LDL may play a causative role to produce the insulin resistance by inhibiting insulin binding, internalization and recycling of insulin receptor in cultured bovine aortic endothelial cells 2. This study suggests that the effect of oxidized LDL to the bovine aortic endothelial cells in insulin binding and receptor-mediated transcytosis is caused by inhibiting pertussis toxin sensitive Gi-protein.
A Case of Insulin Dependent Diabetes Mellitus with MELAS Syndrome Associated with a Mutation of Mitochondrial DNA.
Min Ho Choi, Hyun Mi Rhim, Ki Won Oh, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Hyun Chul Lee, Kap Bum Huh
Korean Diabetes J. 1999;23(2):207-214.   Published online January 1, 2001
  • 1,120 View
  • 22 Download
AbstractAbstract PDF
Mitochondrial mutations are associated with a wide range of disorders (Kearns-Sayre and chronic progressive external ophthalmoplegia syndromes, Myoclonic epilepsy and ragged-red fibre disease, Mitoehondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, Leighs disease ancl cerebellar ataxia plus pigmentary retinopathy syndromes), which is inherited maternally. A-to-G mutation at nuclcotide position 3243 was originally identified in MEI.AS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and accounted for about 80% of the MELAS cases, Recently, this mutation was reported in maternally inherited NIDDM patients. It was also repoded that approximatedly 1% of diabetic patients have this mutation. We performed the molecular genetic analysis of mtDNA in one female insulin dependent diabetic patient with MELAS syndrome and her family members, and also confirmed the A-to-G mutation at nucleotide 3243 of the mtRNA Leu(UUR) gene in their family members.
Effect of Hyperglycemia on Internalization of Insulin-receptor Complexes in Human Umbilical Vein Endothelial Cells.
Ki Ho Song, Yu Bae Ahn, Je Ho Han, Soon Jip Yoo, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 1999;23(2):131-141.   Published online January 1, 2001
  • 1,198 View
  • 27 Download
AbstractAbstract PDF
BACKGROUND
It is well known that hyperglycemia activates protein kinase C (PKC) in vascular endothelial cells. However, the effect of hyperglycemia on internalization and recycling of insulin receptors by insulin in endothelial cells has not been examined thus far. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated from healthy, pregnant women. Confluent HUVECs were incubated in a culture media containing either 5 (NG group) or 25 mM glucose (HG group) for 4 days. Then, we measured the insulin binding, internalization and recycling of the insulin receptor and release of internalized insulin into the media. RESULTS: There was no difference in binding of 0.17 nM 125I-insulin between the two groups. However, the amount of internalized 125I-insulin, determined by the aeid washing method, was significantly greater in the HG group compared to the NG group. The addition of 10 pM 1-(5-isoquino-linesulfonyl)-2-methyl-piperazine (H7), a PKC inhibitor, to the HG group prevented the increase of internalization in 125I-insulin. In addition, preincubation with unlabeled insulin resulted in a decrease of 125I-insulin binding to a greater extent in the HG group compared with the NG group, indicating that high glucose levels increased internalizntion of insulin receptors. The high glucose-induced increase in internalization of insulin receptors was prevented by an addition of H7. Recycling of insulin receptors to the cell surface was not affected by high glucose. Internalized 125I-insulin released into media with time. The released amount of I-insulin in the HC group tended to be greater compared to the NG group. CONCLUSION: These results suggest that hyperglycemia may increase internalization of the insulin-receptor complexes in vascular endothelial cells through PKC activation.
Fasting Serum Insulin Levels in Relation to Age and Body Mass Index and Serum Glucose Level in Healthy Subjects in Korea.
Sang Ah Chang, Ho Young Son, Bong Yun Cha, Sung Dae Moon, Ki Ho Song, Soon Jib Yoo, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Sung Ku Kang
Korean Diabetes J. 1997;21(4):433-443.   Published online January 1, 2001
  • 1,388 View
  • 41 Download
AbstractAbstract PDF
BACKGROUND
Ethnic variability in the relationship between glucose tolerance and insulin secretion has been reported. Clinical characteristics of Korean diabetic patients are different from that of diabetic patients in Western countries. It is generally assumed that typical IDDM or obese diabetic patients are relatively rare among Korean subjects. This study attempted to define the characteristics of fasting serum insulin levels of healthy Korean adult subjects. Futhermore, we tried to evaluate the relationship between fasting serum insulin level and age, body mass index, serum glucose. METHODS: We examined 1917 Korean subjects who had fasting blood glucose within normal range (3.6~6.4mmol/L). The fasting insulin levels, total choiesterol, triglyceride concentrations and anthropometric characteristics(body weight, height and body mass index(BMI)) of these subjects were measured. RESULTS: 1) Mean fasting insulin levels were 33.9+0.5pmol/ L, the fasting insulin levels in men and women were 34.9+0.6 and 31.8+0.6pmol/L, respectively. 2) The fasting insulin levels of obese(BMI>25) subjects were significantly higher than those of non-obese subjects(43.2+ 1.2 pmol/L vs. 30.6+0.6 pmol/L, p<0.001). 3) There were significant differences in the basal insulin levels among the age groups, and fasting blood glucose levels were increased with aging. 4) In a multiple stepwise regression analysis, insulin levels were positively correlated with serum triglycerides, fasting blood glucose, body mass index and negatively correlated with age. Conclusion : The fasting insulin levels of healthy subjects in Korea were relatively lower than the previously measured value of Caucasians. The insulin levels were decreased with aging and increased with the elevation of BMI, fasting blood glucose and triglyceride.
The Effect of Metformin Monotherapy in Patients with NIDDM.
Yu Bae Ahn, Sung Dae Moon, Sang Ah Jang, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 1997;21(2):185-193.   Published online January 1, 2001
  • 1,225 View
  • 26 Download
AbstractAbstract PDF
BACKGROUND
We performed this study to investigate the effect of metformin on glycemia, insulin secretion and body weight in patients with non-insulin-dependent diabetes melltus(NIDDM) who could not aehieve satisfactory glycemic control by sulfonylurea or diet therapy. METHODS: A total of 167 patients with NIDDM were included in this study. At baseline the patients underwent anthropometry and a 75g oral glucose tolerance test. Jn addition, levels of hemoglobin Alc (HbAlc), setum lipids, fasting and postprandial 2hr glucose were measured. Metformin was given in an initial dose of 500mg twice daily and increased by 500mg every month as long as the fasting blood sugar(FBS) concentration exceeded 7.8mmol/L and the side effects were tolerable. After 3 rnonths of metformin therapy we defined a responder as a patient who experienced a FBS of under 7.8 mmol/L or a HbAlc of under 7%. Patients who failed to respond to metformin monotherapy were excluded in the study. Anthrapometric changes and results of a 75 g oral glucose tolerance test were reevaluated in the responder group after 6 months of metformin treatment. RESULTS: I) The overall response rate to metformin mono-therapy was 55.6%(79/142) in the study population. 2) There were significant changes in body weight (64.4+/-8.2 vs 62.9+/-8.4 kg, p(0.01) and body mass index(25.3+/-2.3 vs 24.6+/-2.3kg/m, p<0.01) during metformin treatment. 3) There were significant decreases in the fasting, postprandial 2hr serum glucose(10.1+/-2.8 vs 7.9+1.6, 15,2+/-5.0 vs 12.2+/-3.9 mmol/L, p 0.01) and HbAlc levels(8.4+/-1.7 vs 6.5+/-0.9%, p<0.05) after 6 months of metformin treatment. 4) There were significant decreases in the levels of AUC[g](59.2+/-15.5 vs 49.4+/-9.4mmol L-1. Min-1, p =C0.01) without changes of AUC[I] and AUC[I]/ AUC[g] ratio (558.0+486.0 vs 536.4+374.4 pmol.L-1. Min-1, p=0.71, 11.7+/-13.0 vs 11.8+/-10.0, p=0.89). 5) The incidence of side effects was 25% in the study population, but most of them were mild and fade away with continuous use of metformin, CONCLUSION: Metforrnin monotherapy improved glycemic control in NlDDM patients who failed to respond to diet or sulfonylurea therapy and may be a useful hypoglycemic agent for the treatment of NIBDM.
Case reports on diabetes mellitus caused by malnutrition-related diabetes mellitus and chronic relapsing pancreatitis.
Yong Joo Kim, Jong Min Lee, Hyun Shik Son, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang, Young Taek Song, Sang In Shim
Korean Diabetes J. 1992;16(4):341-346.   Published online January 1, 2001
  • 980 View
  • 23 Download
AbstractAbstract PDF
No abstract available.
3 cases of emphysematous pyelonephritis complicated in diabetics.
Jong Min Lee, Seung Ho Bang, Chae Ho Han, Hyun Shik Son, Kun Ho Yoon, Sung Ku Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son
Korean Diabetes J. 1992;16(4):335-340.   Published online January 1, 2001
  • 1,053 View
  • 18 Download
AbstractAbstract PDF
No abstract available.
Prevalence of micro and macroalbuminuria in relation to hypertension and chronic diabetic vascular complications among type II diabeticpatients.
Hyuk Ho Kwon, Je Ho Han, Jong Min Lee, Soon Jip Yoo, Hyun Sik Son, Kun Ho Yoon, Moo Il Kang, Jwan Soo Hong, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang
Korean Diabetes J. 1992;16(4):317-324.   Published online January 1, 2001
  • 1,062 View
  • 18 Download
AbstractAbstract PDF
No abstract available.
Effect of calcium upon insulin inhibition induced by hydrocortisonein perfused rat pancreas.
Kun Ho Yoon, Soon Jib Yoo, Hyun Sik Son, Moo Il Kang, Kwan Soo Hong, Bong Youn Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 1991;15(2):205-212.   Published online January 1, 2001
  • 944 View
  • 18 Download
AbstractAbstract PDF
No abstract available.
Diabetic isolated oculomotor nerve palsy with loss of the papillaryreflex.
Ji Youn Han, Kun Ho Yoon, Hoon Kyo Kim, Kwang Woo Lee, Ho Young Son, Sung Ku Kang
Korean Diabetes J. 1991;15(1):145-148.   Published online January 1, 2001
  • 753 View
  • 16 Download
AbstractAbstract PDF
No abstract available.
Relationship between magnesium and calcium to glucose stimulated insulin secretion in the perfused rat pancreas.
Kun Ho Yoon, Soon Jip Yoo, Hyun Sik Son, Moo Il Kang, Kwan Soo Hong, Bong Youn Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang
Korean Diabetes J. 1991;15(1):63-71.   Published online January 1, 2001
  • 993 View
  • 19 Download
AbstractAbstract PDF
No abstract available.

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer
TOP