Diabetes & Metabolism Journal

Volume 30(4); July 2006

Review

Rho-kinase and Insulin Signaling.: Young Bum Kim; Korean Diabetes J. 2006;30(4):237-245. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.237

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Abstract PDF: Insulin's ability to acutely stimulate glucose uptake and metabolism in peripheral tissues is essential for normal glucose homeostasis. Resistance to this insulin effect is a major pathogenic feature of type 2 diabetes and obesity. Although many of the proximal steps in insulin signaling have been identified, the molecular mechanisms underlying insulin resistance under various metabolic states are still unclear. Recent study suggests that Rho-kinase is an important mediator of insulin signaling and glucose homeostasis. Specifically, Rho-kinase directly controls insulin receptor substrate-1, which plays an important role in regulating insulin action. Inhibition of Rho-kinase function results in a decreased insulin response, leading to insulin resistance. Thus, Rho-kinase is identified as a novel regulator of insulin action and glucose homeostasis, and a potential target for new diabetes drugs.

Original Articles

Glucose Oxidation and Production of Reactive Oxygen Species (ROS) in INS-1 Cells and Rat Islet Cells Exposed to High Glucose.: Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2006;30(4):246-253. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.246

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Abstract PDF

BACKGROUND
Chronic exposure of pancreatic islets to supraphysiologic concentrations of glucose causes beta cell dysfunction that is a process known as glucose toxicity. It has been reported that hyperglycemia increases the production of reactive oxygen species (ROS) in human islets and that ROS accumulation causes beta cell dysfunction associated with low capacity of intrinsic antioxidant enzymes. Also it has been postulated that this increase in ROS is prevented by an inhibitor of electron transport chain complex. The purpose of this study were to determine whether prolonged exposure of pancreatic islets to supraphysiologic glucose concentrations disrupts the intracellular balance between ROS thereby causing defective insulin secretion and to evaluate the site of hyperglycemia-induced ROS production. METHODS: INS-1 cells & rat islets were incubated in increasing concentrations of glucose and either an inhibitor of complex I & II (TTFA), an uncoupler of oxidative phosphorylation (CCCP), aCCA, etc and also incubated in increasing concentration of glyceraldehyde and N-acetylcystein. Then intracellular peroxide levels by flow cytometric analysis and glucose induced insulin secretion were detected. RESULTS: We observed that incubation with 30 mM glucose increased intracellular peroxide levels but decreased glucose-stimulated insulin secretion (GSIS) (P < 0.05). Exposure to TTFA, CCCP, aCCA did not reduce this increased intracellular peroxide levels, and did not increase GSIS (P < 0.05). 24-h incubation with glyceraldehyde at 5.6 mM glucose increased intracellular peroxide levels and decreased insulin content. CONCLUSION: These observations indicate that there might be other origins in which ROS species are produced besides electron transport chain in mitochondria and glyceraldehyde may be a key molecule to produce ROS, and induce beta cell dysfunction.

Citations

Citations to this article as recorded by

Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors—A review
Abdur Rauf, Anees Ahmed Khalil, Samir Awadallah, Shahid Ali Khan, Tareq Abu‐Izneid, Muhammad Kamran, Hassan A. Hemeg, Mohammad S. Mubarak, Ahood Khalid, Polrat Wilairatana
Food Science & Nutrition.2024; 12(2): 675. CrossRef
The Protective Effects of Chrysanthemum cornarium L. var. spatiosum Extract on HIT-T15 Pancreatic β-Cells against Alloxan-induced Oxidative Stress
In-Hye Kim, Kang-Jin Cho, Jeong-Sook Ko, Jae-Hyun Kim, Ae-Son Om
The Korean Journal of Food And Nutrition.2012; 25(1): 123. CrossRef

The Effect of High Glucose and TGF-beta on the Cellular Injury in Cultured Glomerular Epithelial Cells.: Gui Hwa Jeong, Sung Chang Chung, Eui Dal Jung, Yun Jeong Doh, Hee Kyoung Kim, Soon Hong Park, In Hae Park, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim, In Kyu Lee, Cheol Woo Ko; Korean Diabetes J. 2006;30(4):254-263. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.254

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Abstract PDF: BACKGROUND
The glomerulus is a complex physiological structure, as well as selective filtration barrier in the control of renal blood flow and blood pressure. Glomerular epithelial cells may play an important role in development of diabetic nephropathy. Apoptosis of the glomerular epithelial cells are characterized by disappearance of a selective filtration barrier. TGF-beta is a key factor in the development of diabetic nephropathy because of its effects on the accumulation of extracellular matrix and mesangial cell proliferation. We examined whether the high glucose and TGF-beta induce the apoptosis in cultured rat glomerular epithelial cells. METHODS: Glomerular epithelial cells were cultured from rat glomeruli and conditioned with different concentration of TGF-beta or high-glucose. We measured apoptosis of cultured rat glomerular epithelial cell conditioning with different concentration of TGF-beta or high-glucose by using DNA electrophoresis. RESULTS: High glucose (25 mM) induced apoptosis of cultured rat glomerular epithelial cells compared to controls. TGF-beta also induced cell death of cultured rat glomerular epithelial cells in dose dependent manner. CONCLUSION: These results suggest that high glucose and TGF-beta-induced cell death of glomerular epithelial cell may play an important role in diabetic nephropathy and proteinuria. Pathway of apoptosis or cell death by high glucose and TGF-beta must be investigated in the glomerular epithelial cells.

Long-term Effect of Pioglitazone Treatment in Patients with Type 2 Diabetes.: Jae Hoon Moon, Hye Jin Kim, Soo Kyung Kim, Wan Sub Shim, Eun Seuk Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(4):264-276. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.264

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Abstract PDF

BACKGROUND
Type 2 diabetes is characterized by impaired insulin secretion and/or insulin resistance. Thiazolidinediones have been shown to ameliorate insulin resistance. The purpose of the present study was to evaluate the long term serial effect of pioglitazone on anthropometrics and metabolic parameters in Korean type 2 diabetes patients. METHODS: One hundred thirteen type 2 diabetes patients (male, 67; female, 46; mean age, 49.1+/-10.8 years) were evaluated before and after 3 months, 6 months and 12 months of treatment with pioglitazone (Actos(TM), 15 mg/day). Anthropometric parameters and metabolic variables were measured. RESULTS: Body weight and body mass index (BMI) were increased in 3 months after pioglitazone treatment (body weight, 68.8+/-12.2 vs 69.8+/-11.9 kg, P < 0.01) without further increase. In women, body weight and BMI tended to increase more (body weight change after 3 months, 0.6+/-1.7 kg vs 1.6+/-1.7 kg, P < 0.01) and longer (3 months vs 6 months) than in men. Fasting plasma glucose (FPG) and HbA1c were decreased in 3 months after pioglitazone treatment (FPG, 7.97+/-2.29 vs 6.94+/-2.01 mmol/L, P < 0.01; HbA1c, 7.7+/-1.5 vs 7.0+/-1.1%, P < 0.01). Hypoglycemic effect of pioglitazone was prominent in women than in men (FPG change after 12 months, -1.80+/-2.54 vs -0.09+/-1.72 mmol/L, P < 0.001; HbA1c change after 12 months, -0.9+/-1.3 vs -0.4+/-1.1%, P < 0.05). Serum high-density lipoprotein cholesterol was increased after 3 months of pioglitazone treatment (1.16+/-0.24 vs 1.31+/-0.28 mmol/L, P < 0.01) without return until the end of this study. Serum triglycerides level decreased at 3 months (basal vs 3 months, 2.29+/-1.86 vs 1.88+/-1.21 mmol/L, P < 0.01) and 6 months (basal vs 6 months, 2.29+/-1.86 vs 1.97+/-1.40 mmol/L, P < 0.05) of pioglitazone treatment, but returned to basal level at 12 months. Liver enzyme, especially serum alanine transferase level decreased after 3 months of pioglitazone treatment (30.8+/-23.7 vs 24.5+/-18.5 IU/L, P < 0.01) without return until the end of this study. Hypoglycemic effect of pioglitazone was associated with basal BMI, fat contents and serum leptin level. CONCLUSION: Korean type 2 diabetes patients with pioglitazone use showed favorable metabolic effect for glycemic control, lipid metabolism and liverfunction, but pioglitazone induced body weight increase may be limited.

Citations

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Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations
Won Sang Yoo, Do Hee Kim, Hee Jin Kim, Hyun Kyung Chung
The Journal of Korean Diabetes.2019; 20(2): 117. CrossRef

Usefulness of Insulin Sensitivity Indexes derived from Oral Glucose Tolerance Test in Women with Polycystic Ovary Syndrome.: Hyo Jeong Kim, Eun Kyung Byun, Jee Young Oh, Yeon Ah Sung, Hye Won Chung; Korean Diabetes J. 2006;30(4):277-284. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.277

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Abstract PDF

BACKGROUND
Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and it makes them to have high risk for development of type 2 diabetes. Evaluation of insulin sensitivity would be important to predict their risks. Although the euglycemic-hyperinsulinemic clamp technique is the gold standard for measuring insulin sensitivity, it is too hard to practice in large epidemiologic studies. The aim of this study is to verify the validity of various insulin sensitivity indexes from oral glucose tolerance test (OGTT) in women with PCOS. METHODS: We performed euglycemic-hyperinsulinemic clamp (target glucose; 90 mg/dL, insulin ;~1 mU/kg.min) to obtain insulin-mediated glucose disposal rate (M-value) in 62 non-diabetic women with PCOS (BMI < 23 kg/m2; n = 37, BMI > or = 23 kg/m2; n = 25). Homeostasis model assessment [HOMA(IR)], quantitative insulin sensitivity check index (QUICKI), glucose to insulin ratio (G/I ratio), whole body insulin sensitivity index [ISI(COMP)], metabolic clearance rate of glucose [MCR(est)-OGTT(1,2)], and insulin sensitivity indexes [ISI(est)-OGTT(1,2)] were calculated from plasma glucose and insulin levels from standard 75-g OGTT. The correlations of various insulin sensitivity indexes from OGTT with M-value were evaluated. RESULTS: In lean women with PCOS (BMI < 23 kg/m2, n = 37), ISI(COMP) (r = 0.36, P < 0.05), MCRest-OGTT1 (r = 0.49, P < 0.01), ISI(est)-OGTT(1) (r = 0.50, P < 0.01), MCR(est)-OGTT(2) (r = 0.45, P < 0.01) and ISI(est)-OGTT(2) (r = 0.40, P < 0.05) were significantly correlated with M-value. In overweight and obese women with PCOS (BMI > or = 23 kg/m2, n = 25), HOMA(IR) (r = -0.40, P < 0.05), QUICKI (r = 0.40, P < 0.05), MCR(est)-OGTT(1) (r = 0.76, P < 0.001), ISI(est)-OGTT(1) (r = 0.63, P < 0.001), MCR(est)-OGTT(2) (r = 0.58, P < 0.01) and ISI(est)-OGTT(2) (r = 0.42, P < 0.05) showed significant correlations with M-value. CONCLUSION: MCR(est)-OGTT(1) and ISI(est)-OGTT(1) were the most reliable and easily accessible insulin sensitivity indexes obtained from OGTT for measuring of insulin sensitivity in women with PCOS regardless of obesity.

Citations

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Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes
Flavia Tosi, Enzo Bonora, Paolo Moghetti
Human Reproduction.2017; 32(12): 2515. CrossRef

Prevalence of Metabolic Syndrome in Young Korean Women with Polycystic Ovary Syndrome.: Hyejin Lee, Jee Young Oh, Youngsun Hong, Yeon Ah Sung, Hyewon Chung; Korean Diabetes J. 2006;30(4):285-291. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.285

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Abstract PDF

BACKGROUND
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and consequent hyperinsulinemia. Insulin resistance plays an important role in the development of metabolic syndrome (MS). We conducted a cross-sectional study to determine the prevalence of the MS and whether the insulin resistance or hyperandrogenemia is related to the MS in young Korean women with PCOS. METHODS: 143 women with PCOS (mean age 26+/-5 years) were studied to evaluate the prevalence of MS by modified Adult Treatment Panel III. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp technique. RESULTS: The prevalence of MS in women with PCOS was 11.9%, 2.8-fold higher than age matched women in Korean urban population. The most frequent component of MS was low HDL cholesterol (39.4%), and the least frequent one was high fasting serum glucose levels (6.7%). The frequency of MS was 40.7% in obese PCOS (BMI > or = 25 kg/m2, n = 38), 10.0% in overweight PCOS (BMI 23~24.9 kg/m2, n = 13), and 0% in lean PCOS (BMI < 23 kg/m2, n = 92). The frequency of MS was 26.1% in insulin resistant PCOS (insulin mediated glucose uptake, IMGU < lowest 10th percentile of lean controls, n = 65), whereas no one had MS in insulin sensitive PCOS (IMGU > or = lowest 10th percentile of lean controls, n = 78). CONCLUSION: MS is frequent in young women with PCOS, and obesity and insulin resistance might be essential for the development of MS in this study group.

Citations

Citations to this article as recorded by

Relationship between flavonoids intake and metabolic syndrome in Korean women with polycystic ovary syndrome
Ji Soo Oh, Mi Jin Ahn, Chan Jung Han, Hyesook Kim, Oran Kwon, Hye Won Chung, Namsoo Chang
Journal of Nutrition and Health.2014; 47(3): 176. CrossRef
Inappropriate gonadotropin secretion in polycystic ovary syndrome: The relationship with clinical, hormonal and metabolic characteristics
A Ra Shim, Yu Im Hwang, Kyung Jin Lim, Young Mi Choi, Young Eun Jeon, Seok Kyo Seo, Si Hyun Cho, Young Sik Choi, Byung Seok Lee
Korean Journal of Obstetrics & Gynecology.2011; 54(11): 659. CrossRef
Diagnosis and Treatment of Polycystic Ovary Syndrome
Hyejin Lee, Yeon-ah Sung
Journal of Korean Endocrine Society.2007; 22(4): 252. CrossRef

Efficacy Evaluation of Atorvastatin in Korean Hyperlipidemic Patients with Type 2 Diabetes Mellitus.: Dong Seop Choi, Duk Kyu Kim, Doo Man Kim, Seong Yeon Kim, Moon Suk Nam, Yong Soo Park, Ho Sang Shon, Chul Woo Ahn, Kwan Woo Lee, Ki Up Lee, Moon Kyu Lee, Choon Hee Chung, Bong Yeon Cha; Korean Diabetes J. 2006;30(4):292-302. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.292

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Abstract PDF

BACKGROUND
NCEP ATP III Guideline recommends aggressive treatments of diabetic dyslipidemia, recognizing diabetes mellitus as CHD risk equivalents. This study was conducted to evaluate the effectiveness and safety of atorvastatin in hyperlipidemic patients with Type 2 diabetes mellitus through post-marketing drug use investigation of atorvastatin. METHODS: An open, multi-center, non-comparison, titrated dosage study was conducted in hyperlipidemic patients, who were treated with atorvastatin at first visiting hospitals from Mar. 2004 to Sep. 2004. 96 endocrinologists participated from 66 centers in this study. Total 2,182 hyperlipidemic patients were enrolled and 1,514 patients among them were accompanied by diabetes mellitus. Efficacy was evaluated at later than 4-week treatment by % change of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol from baseline. Percent of patients reaching LDL-cholesterol level less than 100 mg/dL was also analyzed. The adverse events incidence and abnormalities of clinical laboratory values were evaluated for safety monitoring. RESULTS: Total cholesterol, triglycerides, and LDL-cholesterol level were reduced by 26.6%, 12.0%, and 34.8%, respectively, in diabetic hyperlipidemic patients after atorvastatin treatment. The patients with LDL-cholesterol level of less than 100 mg/dL were increased from 2.8% to 52.6%. Atorvastatin was considered to be safe because adverse drug reactions were reported in 32 patients (1.5%) of total 2,182 patients. CONCLUSION: Atorvastatin was effective and safe in hyperlipidemic patients with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by

Response: A Retrospective Study on the Efficacy of a Ten-Milligram Dosage of Atorvastatin for Treatment of Hypercholesterolemia in Type 2 Diabetes Mellitus Patients (Korean Diabetes J 2010;34:359-67)
Dong Kyun Kim, Sa Rah Lee, Min Sik Kim, Suk Hyang Bae, Jin Yeon Hwang, Jung-Min Kim, Sung Hwan Suh, Hye-Jeong Lee, Mi Kyoung Park, Duk Kyu Kim
Diabetes & Metabolism Journal.2011; 35(1): 88. CrossRef
A Retrospective Study on the Efficacy of a Ten-Milligram Dosage of Atorvastatin for Treatment of Hypercholesterolemia in Type 2 Diabetes Mellitus Patients
Dong Kyun Kim, Sa Rah Lee, Min Sik Kim, Suk Hyang Bae, Jin Yeon Hwang, Jung-Min Kim, Sung Hwan Suh, Hye-Jeong Lee, Mi Kyoung Park, Duk Kyu Kim
Korean Diabetes Journal.2010; 34(6): 359. CrossRef
The Association of Plasma HDL-Cholesterol Level with Cardiovascular Disease Related Factors in Korean Type 2 Diabetic Patients
Hye Sook Hong, Jong Suk Park, Han Kyoung Ryu, Wha Young Kim
Korean Diabetes Journal.2008; 32(3): 215. CrossRef

Value of Coronary Calcium Score in Type 2 Diabetics.: Ji Eun Lee, Mi Jung Eun, Kyung Ah Chun, Jae Hong Kim, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2006;30(4):303-311. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.303

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Abstract PDF: BACKGROUND
Cardiovascular disease including coronary heart disease (CHD) is the most common cause of morbidity and mortality in patients with diabetes. But traditional risk factor assessment is limited to predict CHD in asymptomatic high-risk individuals. In this study, relationship between coronary calcium score (CCS) and CHD was evaluated to determine value of coronary artery calcification detected by multi-slice spiral computed tomography to predict CHD in high risk asymptomatic patients with type 2 diabetes. METHODS: 127 patients were enrolled who admitted in Yeungnam University Hospital between December 2004 and May 2005. Standard cardiovascular risk factors and the CCS measured by multi-slice spiral computed tomography were assessed. RESULTS: Enrolled subjects were consisted of 56 subjects with diabetes and 71 subjects without diabetes. The mean CCS was significantly greater in patients with diabetes than without diabetics (P < 0.01). In both groups, patients with higher CCS had higher prevalence of CHD (P < 0.05). In all subjects, LDL cholesterol levels and CCS were significantly associated in multi-variate analysis (P < 0.05). In patients without diabetes, age was only associated with presence of CHD (P < 0.05). CCS was only associated with CHD in patients with diabetes, even after adjusting for the effects of age, LDL cholesterol and CRP (P < 0.05). CONCLUSION: Therefore, multi-slice spiral computed tomography can non-invasively and accurately detect coronary calcification. By detection of coronary artery calcification, it may be possible to predict coronary heart disease early in high-risk asymptomatic patients with type 2 diabetes.

Case Report

A Case of Acromegaly Presenting with Diabetic Ketoacidosis.: Jin Dong Kim, Tae Seo Sohn, Jee In Lee, Jick Hwan Hah, Yun Hwa Jung, Jung Min Lee, Sung Min Nam, Seung Won Lee, Hyun Shik Son; Korean Diabetes J. 2006;30(4):312-315. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.312

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Abstract PDF: In patients with acromegaly, glucose intolerance and diabetes mellitus are one of the frequent manifestations. And the type of diabetes in these patients is usually non-insulin dependent type secondary to insulin resistance caused by growth hormone excess. Therefore, the diabetes mellitus in these patients dose not tend to develop diabetic ketoacidosis. But we experienced and presented the case of a patient with acromegaly hospitalized due to the diabetic ketoacidosis without overt clinical manifestations of acromegaly. This case of acromegaly showed that growth hormone excess could cause diabetic ketoacidosis in the presence of relative insulin deficiency.

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