Diabetes & Metabolism Journal

In Kyu Lee (Lee IK)

38 Articles

The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.: Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim; Korean Diabetes J. 2009;33(6):485-493. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.485

2,648 View
34 Download
2 Crossref

BACKGROUND
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.

Citations

Citations to this article as recorded by

The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
Tae Kyung Yoo, Mi Yeon Lee, Ki-Chul Sung
Journal of Atherosclerosis and Thrombosis.2024; 31(8): 1194. CrossRef
Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
Ki Won Oh
Korean Diabetes Journal.2009; 33(6): 464. CrossRef

Leptin is Negatively Associated with Femoral Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes Mellitus.: Jae Han Jeon, Yeun Kyung Choi, Hyun Ae Seo, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, Ju Young Lee, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2009;33(5):421-431. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.421

2,407 View
20 Download
1 Crossref

Abstract PDF

BACKGROUND
Serum leptin level and bone mineral density (BMD) are widely assumed to be positively associated with body fat mass. Numerous attempts have been made to document the relationship between leptin and BMD, but the results are inconsistent, especially in diabetic patients. METHODS: A total of 60 Korean postmenopausal women with type 2 diabetes mellitus were included in the present study. The BMDs of lumbar spines (L1 to L4) and proximal femurs (trochanter, neck, and total) were measured by dual-energy X-ray absorptiometry (DXA), and biochemical markers including leptin, HbA1c, C-peptide and urine albumin-creatinine ratio (ACR) were measured for each patient. RESULTS: Negative associations between leptin and BMD of femoral neck, trochanter, and total femur in postmenopausal women with type 2 diabetes mellitus were documented in a model adjusted for age, body fat mass, and fasting insulin level (r = -0.308, P = 0.020 and r = - 0.303, P = 0.025 and r = - 0.290, P = 0.032 respectively). Multiple linear regression analysis was performed revealing negative associations between leptin and BMD of the femoral neck (beta = -0.369), trochanter (beta = -0.324), and total femur (beta = -0.317). CONCLUSION: The results of the present study suggest a negative relationship between leptin and femoral BMD. In addition, leptin may have a negative effect on BMD in postmenopausal women with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by

Evaluation of bone mineral density in type 2 diabetes mellitus patients before and after treatment
MK Dutta, R Pakhetra, MK Garg
Medical Journal Armed Forces India.2012; 68(1): 48. CrossRef

The Association Between Urinary Albumin to Creatinine Ratio and Coronary Artery Calcification in Type 2 Diabetic Patients.: Ju Young Lee, Yeon Kyung Choi, Hyun Ae Seo, Jae Han Jeon, Jung Eun Lee, Seong Su Moon, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2009;33(4):289-298. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.289

2,364 View
28 Download

Abstract PDF: BACKGROUND
Atherosclerosis, the most common cause of death in type 2 diabetic patients, is closely associated with coronary artery calcium deposition. The coronary calcifications can be easily measured using coronary calcium scoring computed tomography (CT). And microalbuminuria is known as an independent risk factor of cardiovascular disease. So, we examined the association of urinary albumin to creatinine ratio (UACR) and coronary calcification score (CCS) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who underwent the multidetector CT scanning for the evaluation of CCS at Kyungpook National University Hospital between December 2007 and May 2008, 155 subjects were included. CCS, demographic and laboratory data were assessed. RESULTS: Coronary artery calcifications were identified in 90 patients (51%) and mean, median CCS was 205.8 +/- 476.9, 8.74 (0, 132.0). 60 subjects revealed UACR greater than 30 ug/mg. With the UACR increment, CCS revealed a significant increase (P < 0.001). Age, duration of diabetes, serum Apo A1 level, serum high sensitivity C-reactive protein (hs-CRP) level were also associated with CCS. However, after adjusting for age, UACR and CCS exhibited a significant positive relationship (P = 0.002). CONCLUSION: Increased UACR is associated with coronary artery calcification in type 2 diabetic patients and these results will be useful in early evaluating the presence of macrovascular complications in these patients.

Effect of Adipose Differentiation-Related Protein (ADRP) on Glucose Uptake of Skeletal Muscle.: Yun Hyi Ku, Min Kim, Sena Kim, Ho Seon Park, Han Jong Kim, In Kyu Lee, Dong Hoon Shin, Sung Soo Chung, Sang Gyu Park, Young Min Cho, Hong Kyu Lee, Kyong Soo Park; Korean Diabetes J. 2009;33(3):206-214. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.206

2,313 View
33 Download

Abstract PDF: BACKGROUND
Skeletal muscle is the most important tissue contributing to insulin resistance. Several studies have shown that accumulation of intramyocellular lipid is associated with the development of insulin resistance. Thus, proteins involved in lipid transport, storage and metabolism might also be involved in insulin action in skeletal muscle. Adipose differentiation-related protein (ADRP), which is localized at the surface of lipid droplets, is known to be regulated by peroxisome proliferator activated receptor gamma (PPARgamma). However, it is not known whether ADRP plays a role in regulating glucose uptake and insulin action in skeletal muscle. METHODS: ADRP expression in skeletal muscle was measured by RT-PCR and western blot in db/db mice with and without PPARgamma agonist. The effect of PPARgamma agonist or high lipid concentration (0.4% intralipos) on ADRP expression was also obtained in cultured human skeletal muscle cells. Glucose uptake was measured when ADRP was down-regulated with siRNA or when ADRP was overexpressed with adenovirus. RESULTS: ADRP expression increased in the skeletal muscle of db/db mice in comparison with normal controls and tended to increase with the treatment of PPARgamma agonist. In cultured human skeletal muscle cells, the treatment of PPARgamma agonist or high lipid concentration increased ADRP expression. siADRP treatment decreased both basal and insulin-stimulated glucose uptake whereas ADRP overexpression increased glucose uptake in cultured human skeletal muscle cells. CONCLUSION: ADRP expression in skeletal muscle is increased by PPARgamma agonist or exposure to high lipid concentration. In these conditions, increased ADRP contributed to increase glucose uptake. These results suggest that insulin-sensitizing effects of PPARgamma are at least partially achieved by the increase of ADRP expression, and ADRP has a protective effect against intramyocellular lipid-induced insulin resistance.

Association of the Polymorphisms in the PSMA6 (rs1048990) and PSMB5 (rs2230087) Genes with Type 2 Diabetes in Korean Subjects.: Hee Kyoung Kim, Su Won Kim, Yun Jeong Doh, Sae Rom Kim, Mi Kyung Kim, Keun Gyu Park, Hye Soon Kim, Kyong Soo Park, Min Yoo, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2008;32(3):204-214. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.204

2,458 View
27 Download
3 Crossref

Abstract PDF

BACKGROUND
The 26S ubiquitin-proteasome system (UPS) is a principal proteolytic pathway of intracellular molecules regulating apoptosis, cell cycle, cell proliferation or differentiation, inflammation and etc. The recent study suggests that the rs1048990 (C/G) polymorphism of the proteasome subunit alpha type 6 (PSMA6) gene is associated with the increase of the risk of myocardial infarction by the dysregulation of IkappaB degradation. We hypothesized that 26S UPS is important in the development of insulin resistance and type 2 diabetes (T2DM) by controlling the degradation of IkappaB and insulin receptor substances as a substrate. We therefore investigated whether the rs1048990 (C/G) polymorphism of PSMA6 gene and the rs2230087 (G/A) polymorphism of proteasome subunit beta type 5 gene (PSMB5), that is chymotrypsin-like protease determining the rate of proteolysis, are associated with susceptibility to T2DM in Korean subjects. METHODS: We examined the polymorphisms of these genes in 309 diabetic subjects and 170 non-diabetic controls. The polymorphisms of rs1048990 (C/G) and rs2230087 (G/A) were genotyped by real-time PCR. RESULTS: The frequency of the G allele of rs1048990 (C/G) and the A allele of rs2230087 (G/A) polymorphisms was significantly higher in diabetic patients (28% and 13%) compared to that in controls (13% and 1%; P = 0.000 and P = 0.000, respectively). Logistic regression analysis of the rs1048990 (C/G) polymorphism showed that the odds ratio (OR) (adjusted for age, smoking, waist circumference, fasting plasma glucose, systolic blood pressure, HDL-C, triglyceride, and total cholesterol) was 3.93 (95% confidence interval [CI], 2.35-6.59; P = 0.000) for the G allele and 5.09 (95% CI, 2.71-9.57; P = 0.000) for CG and GG genotype when compared with the CC genotype. Logistic regression analysis of the rs2230087 (G/A) polymorphism showed that the adjusted OR was 5.70 (95% CI, 1.63-19.98; P = 0.007) for the A allele and 6.08 (95% CI, 1.66-22.29; P = 0.006) for GA and AA genotype when compared with the GG genotype. In multiple logistic regression analysis with T2DM as the independent Variable rs1048990 (C/G) and rs2230087 (G/A) polymorphisms were the predictor for T2DM. CONCLUSION: We suggest that the G allele of rs1048990 (C/G) polymorphism and the A allele of rs2230087 (G/A) polymorphism may be genetic risk factor to type 2 diabetes mellitus in Korean subjects.

Citations

Citations to this article as recorded by

Ubiquitin-proteasome system in diabetic retinopathy
Zane Svikle, Beate Peterfelde, Nikolajs Sjakste, Kristine Baumane, Rasa Verkauskiene, Chi-Juei Jeng, Jelizaveta Sokolovska
PeerJ.2022; 10: e13715. CrossRef
1,4‐Dihydropyridine derivatives without Ca2+‐antagonist activity up‐regulate Psma6 mRNA expression in kidneys of intact and diabetic rats
Kristīne Ošiņa, Evita Rostoka, Jelizaveta Sokolovska, Natalia Paramonova, Egils Bisenieks, Gunars Duburs, Nikolajs Sjakste, Tatjana Sjakste
Cell Biochemistry and Function.2016; 34(1): 3. CrossRef
Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals
Tatjana Sjakste, Natalia Paramonova, Kristine Osina, Kristine Dokane, Jelizaveta Sokolovska, Nikolajs Sjakste
Molecular Genetics and Genomics.2016; 291(2): 891. CrossRef

The Effect of Chronic High Glucose Concentration on Endoplasmic Reticulum Stress in INS-1 Cells.: Mi Kyung Kim, Hye Young Seo, Tae Sung Yun, Nam Kyung Kim, Yu Jin Hah, Yun Jung Kim, Ho Chan Cho, Young Yun Jang, Hye Soon Kim, Seong Yeol Ryu, In Kyu Lee, Keun Gyu Park; Korean Diabetes J. 2008;32(2):112-120. Published online April 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.2.112

2,920 View
36 Download

Abstract PDF: BACKGROUND
The highly developed endoplasmic reticulum (ER) structure is one of the characteristic features of pancreatic beta-cells. Recent study showed that ER stress causes beta-cell dysfunction. However, little is known about the effects of high glucose concentration on induction of ER stress in pancreatic beta-cells. Therefore, this study was designed to evaluate whether exposure of high glucose concentration in rat insulinoma cell line, INS-1 cell induces ER stress and whether ER stress decreases insulin gene expression. METHODS: The effect of 30 mM glucose on insulin expression and secretion in INS-1 cells was evaluated by Northern blot analysis and glucose-stimulated insulin secretion (GSIS). Cell viability was evaluated by XTT assay. The effect of 30 mM glucose on phosphorylation of eIF2alpha and CHOP expression, which are markers of ER stress were evaluated by Western blot analysis. RT-PCR analysis was performed to determine whether high glucose concentration induces XBP-1 splicing. To investigate whether ER stress decreases insulin gene expression, the effect of tunicamycin on insulin mRNA expression was evaluated by Northern blot analysis. RESULTS: The prolonged exposure of INS-1 cells with the 30 mM glucose concentration decreased insulin mRNA expression in a time dependent manner and impaired GSIS while did not influence on cell viability. 30 mM glucose increased phosphorylation of eIF2alpha, XBP-1 splicing and CHOP expression in INS-1 cells. Tunicamycin-treated INS-1 increased XBP-1 splicing and decreased insulin mRNA expression in a dose dependent manner. CONCLUSION: This study showed that prolonged exposure of INS-1 with high glucose concentration induces ER stress and ER stress decreases insulin gene expression. Further studies about underlying molecular mechanism by which ER stress induces beta-cell dysfunction are needed.

Association of Kir6.2 and Peroxisome Proliferator-activated Receptor-gamma (PPARgamma) Polymorphisms with Type 2 Diabetes in Koreans.: Jung Eun Lee, Su Won Kim, Hyun Ae Seo, Jae Han Jeon, Seong Su Moon, Hee Kyung Kim, Yun Jeong Doh, Bo Wan Kim, Jung Guk Kim, Min Yoo, In Kyu Lee; Korean Diabetes J. 2007;31(6):455-464. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.455

2,427 View
19 Download

Abstract PDF: BACKGROUND
The type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Several variants may contribute significantly to the risk of type 2 diabetes conferring insulin resistance of liver, muscle and fat (Pro12Ala) and a relative insulin secretory deficiency (Glu23Lys). In this study, we evaluated the association of Pro12Ala variant of the peroxisome proliferator- activated receptor-gamma and the Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11) with the type 2 diabetes in Korean population. METHOD: This study included 331 subjects consisting of 172 patients with type 2 diabetes and 159 non- diabetic control subjects enrolled from the Kyungpook, Keimyung and Catholic university hospital in Daegu, Korea. We genotyped Kir6.2 (Glu23Lys) and PPARgamma (Pro12Ala) polymorphism and examined their association with the type 2 diabetes. RESULT: In the separate analyses, the Kir6.2 Glu23Lys (P = 0.385) and the PPARgamma Pro12Ala (P = 0.191) polymorphism showed no significant association with type 2 diabetes. In addition, the results of our study showed no evidence of a synergistic interaction between Kir6.2 and PPARgamma gene in each group (P = 0.110, P = 0.276). CONCLUSION: In this study, no association was seen between the genetic polymorphisms of Kir6.2, PPARgamma and type 2 diabetes. However, to clarify whether genetic polymorphisms of these genes contribute to the development of type 2 diabetes, further studies involving larger Korean populations may be needed.

Transcriptional Regulation of Insulin and CXCL10 Gene by Peroxisome Proliferator Activated Receptor gamma Coactivator-1alpha.: Won Gu Jang, In Kyu Lee, Eun Jung Kim, Seong Yeol Ryu, Bo Wan Kim, Jung Guk Kim; Korean Diabetes J. 2007;31(4):326-335. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.326

2,279 View
22 Download

Abstract PDF: BACKGROUND
Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), which act as a coactivator of nuclear receptors and several other transcription factors. This study was performed to evaluate the expressional regulation of insulin and inflammatory response genes by PGC-1alpha. METHODS: Transient transfection assays were performed to measure the promoter activity of the insulin and CXCL10 gene. The insulin gene expression levels in INS-1 cells were determined by Northern blot analysis. Differentially expressed genes by PGC-1alpha overexpression in HASMCs were confirmed using DNA microarray, real-time PCR and Northen blot analysis. RESULTS: Insulin promoter activity and mRNA levels were suppressed by GR and Ad-PGC-1alpha. Northern blot analysis of the INS-1 cells revealed that infection with Ad-PGC-1alpha markedly reduced the amount of insulin mRNA and treatment of Dex enhanced this effect in an additive manner. The PGC-1alpha-specific siRNA decreased insulin expression that was induced by Dex in the GR-expressing INS-1 cells was nearly restored by this siRNA treatment. We found that when vascular smooth muscle cells (VSMCs) overexpressed PGC-1alpha, immune or inflammatory response genes were highly expressed. For example, promoter activity and mRNA level of CXCL10 gene were increased by PGC-1alpha. CONCLUSION: PGC-1alpha overexpression inhibited insulin promoter activity in INS-1 cells and enhanced expressions of inflammatory response genes (CXCL10, CXCL11, TNFLSF10) in VSMCs.

The Effect of Alpha-lipoic Acid on the Cell Cycle Arrest and Apoptosis in Rat Vascular Smooth Muscle Cells.: Hye Jin Kim, In Kyu Lee, Young Ho Kim, Soon Young Shin, Young Han Lee, Jung Guk Kim, Bo Wan Kim, Hye Soon Kim, Mi Kyoung Kim, Keun Gyu Park, Seong Yeol Ryu; Korean Diabetes J. 2007;31(3):200-207. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.200

2,372 View
22 Download

Abstract PDF: BACKGROUND
The proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of atheroscelrosis and post-angioplasty restenosis. We previously showed that alpha-lipoic acid (ALA) inhibited neointimal hyperplasia and has potential anti-atherosclerosis effect in rat carotid artery balloon injured model. Here, we investigated whether alpha-lipoic acid inhibited proliferation of cells and induced apoptosis in rat vascular smooth muscle cells. METHODS: VSMCs were treated with ALA under each condition, harvested and protein was extracted. Same amount of protein was loaded into SDS-PAGE and western blot analysis was performed with various cell cycle regulation protein. To examine ALA induce apoptosis in VSMCs, FACS and DNA fragmentation assay were performed. Antioxidant effect of ALA was determined by DCF-DA staining. RESULTS: ALA induced VSMCs cell cycle arrest and induced p21, p27 and p53 proteins. Also ALA induced PTEN expression and AMPK phosphorylation. Increased AMPK phosphorylation reduced Erk-2 phosphorylation and finally arrested cell cycle promotion. The apoptotic effect was also shown by ALA treatment. Also we confirmed that ALA reduced ROS generation in VSMCs. CONCLUSION: The present data suggest that ALA has anti-proliferative effect and arrests cell proliferation. Therefore, ALA may provide new strategies for the prevention of neointimal hyperplasia after angioplasty.

Microarray Analysis of Short Heterodimer Partner (SHP)-induced Changes in Gene Expression in INS-1 Cells.: Eui Dal Jung, Ji Hyun Lee, Won Gu Jang, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2007;31(3):193-199. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.193

1,953 View
22 Download

Abstract PDF: BACKGROUND
Nuclear receptors are involved in the cell growth, development, differentiation, and metabolism. The orphan nuclear receptor SHP which lacks a DNA-binding domain is a negative regulator of nuclear receptor signaling pathways. In pancreas, SHP regulate transcriptional activity of HNF3 and HNF4 through binding them and BETA2 which is involved in beta cell differentiation and insulin production. Here, we examined transcriptional activity changes of genes expressed in beta cell when SHP was overexpressed. METHOD: INS-1 cells of passage number 24 - 30 were prepared. Affimetrix DNA chip was used to examine gene expression in INS-1 cell when SHP was overexpressed. INS-1 cells were infected with adenovirus-SHP to overexpress SHP. To confirm the result of DNA chip, we used real time RT-PCR. RESULT: When SHP was overexpressed by adenovirus-SHP transfection, FXR, Transforming growth factor, beta 2, fructose-1,6-bisphosphatase 2, bone morphogenetic protein 4 genes expression were increased. Contrarily, Activating transcription factor 2, Glycogen synthase kinase 3 alpha, Nur 77, fibroblast growth factor 14 genes expression were decreased. We confirmed DNA microarray analysis by real time RT-PCR. FXR, tribbles homolog 3 (Drosophila), fructose-1,6-bisphosphatase 2, CD36 genes expression were increased in real time RT-PCR. Nur 77 and cAMP response element modulator genes expression were decreased in real time RT-PCR. CONCLUSION: we identified several genes which expression are regulated by SHP in pancreas beta cell. These results help to explain how SHP act in the various metabolism of pancreas beta cell.

Proinflammatory Cytokines and Insulin Resistance in Nonobsese Women with High Body Fat and Low Fat Free Mass.: Young Sung Suh, In Kyu Lee, Dae Hyun Kim; Korean Diabetes J. 2007;31(2):136-143. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.136

1,967 View
24 Download
2 Crossref

Abstract PDF

BACKGROUND
Adipose tissue produces and releases a variety of proinflammatory cytokines. The aim of this study was to investigate whether proinflammatory cytokines are increased and insulin resistance is presented in nonobese women with high body fat and low fat free mass. METHODS: Sixty nonobese adult premenopausal women (body mass index, BMI < 25 kg/m2) were included in this study. Body composition was determined by dual energy absoprtiometry (DXA). Fasting glucose, lipid profiles, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C reactive protein (CRP) and basal insulin were measured. RESULTS: The subjects with high body fat (> or = 30%) had higher CRP levels (P = 0.024), IL-6 levels (P = 0.008), insulin levels (P = 0.003), and homeostasis model assessment-IR (HOMA-IR) (P = 0.020) than those of the subjects with low body fat. In a subset of 32 subjects with high body fat (> or = 30%), the number of subjects with high fat free mass index (FFMI) (> or = 13.5 kg/m2) had higher atherogenic index than that of subjects with low FFMI (FFMI < 13.5 kg/m2) (P < 0.05). IL-6 was correlated with % body fat, fat mass index (FMI), and fat mass (P < 0.05). HOMA-IR was correlated with % body fat and FMI (P < 0.05). To investigate predictors of cytokines and HOMA-IR, multiple regression analysis was used. % body fat was a predictor for IL-6 and, while age and % body fat were predictors of HOMA-IR in study subjects. Conclusions: This study suggests that insulin resistance may be present in nonobese women with high body fat and low fat free mass.

Citations

Citations to this article as recorded by

The Effect of Low Intensity Exercise on Expression of Inflammatory Response and Apoptosis in Rats with Obesity Induced by a High-Fat Diet
Dong-Hun Choi, Joon-Yong Cho
Exercise Science.2018; 27(1): 40. CrossRef
Experiences of Health Related Lifestyles in High Body Fat but Non-obese Female College Students in Korea
Jeongsoo Kim
Osong Public Health and Research Perspectives.2014; 5(1): 68. CrossRef

Blood Leptin, Anthropometric and Biochemical Parameters in Type 2 Diabetics.: Seong su Moon, Jae han Jeon, Jung eun Lee, Soon hong Park, Hee kyung Kim, Jeong yun Doh, Ye dal Jung, In kyu Lee, Bo wan Kim, Jung guk Kim; Korean Diabetes J. 2007;31(1):75-82. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.75

2,359 View
30 Download
1 Crossref

Abstract PDF

BACKGROUND
Leptin is a hormone which is produced in adipose tissue and regulates food intake and body weight. Leptin is known to correlate with body adiposity such as body mass index. Blood leptin concentration is not different between non-diabetics and diabetics. And It affect not only food intake but may be one of the key factors in the developement of insulin resistance. Recent studies suggest a complex relationship between leptin and insulin resistance or insulin. Therefore we examined the relationship between leptin and anthropometric, biochemical parameters, and insulin resistance in type 2 diabetics. METHOD: The study subjects were 144 patients with type 2 diabetes who visited Kyungpook national university hospital. Anthropometric parameters such as body fat mass, soft lean mass, BMI, arm circumference, skin fold thickness of several sites were measured. Percent body fat were calculated from Brozek fomula, body density were calculated from Jackson and Pollock fomula. Fasting blood leptin and metabolic varables such as C-peptide, HbA1C, insulin, HDL, LDL, TG, total cholesterol, FFA, HOMA-IR were measured. The relationships of blood leptin concentration with clinical data were analyzed with SPSS program. RESULT: Blood leptin concentrations were 8.2 +/- 5.39 ng/mL in women with type 2 diabetes and 5.1 +/- 5.55 ng/mL in men with type 2 diabetes (P-value: 0.01). Percent body fat, FFA were higher in women than men but arm circumference, soft lean mass, waist circumference were higher in men than women (P-value < 0.05). Leptin concentration correlated with BMI, percent body fat, insulin, TG, body fat mass, waist circumference, HOMA-IR. And insulin, C-peptide, total cholesterol, TG were also correlated with leptin only in women with type 2 diabetes. Waist circumference and percent body fat were independent variables which influence blood leptin concentration in multiple regression analysis. CONCLUSION: Blood leptin concentrations are related to parameters such as percent body fat, waist circumference, BMI, body fat mass, insulin, TG, HOMA-IR in type 2 diabetics. The relationship between leptin and obesity or HOMA-IR suggests that leptin may be a one of factors in developement of insulin resistance.

Citations

Citations to this article as recorded by

Prognostic Value of Leptin in Terminally Ill Cancer Patients
Ji Hyun Hong, So Jin Lee, Sang Mi Kwak, Youn Seon Choi, June Yeong Lee
The Korean Journal of Hospice and Palliative Care.2012; 15(2): 99. CrossRef

Comparison of the Efficacy and Safety of Glimepiride/Metformin Fixed Combination Versus Free Combination in Patients with Type 2 Diabetes: Multicenter, Randomized, Controlled Trial.: Seung Hwan Lee, In Kyu Lee, Sei Hyun Baik, Dong Seop Choi, Kyong Soo Park, Ki Ho Song, Kwan Woo Lee, Bong Soo Cha, Chul Woo Ahn, Hyoung Woo Lee, Choon Hee Chung, Moon Suk Nam, Hong Sun Baek, Yong Ki Kim, Hyo Young Rhim, Ho Young Son; Korean Diabetes J. 2006;30(6):466-475. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.466

2,592 View
54 Download
2 Crossref

Abstract PDF

BACKGROUND
Failure to manage diabetes mellitus receiving monotherapy increases as the duration of the disease is protracted, and in many cases it becomes inevitable to introduce combined therapies. However, compliance of the patients tends to decrease. We conducted a clinical study to compare the efficacy and safety of preconstituted and fixed combination therapy of glimepiride plus metformin to those of free combination therapy. METHODS: Two hundred and thirteen patients with type 2 diabetes who had been diagnosed at least six months ago were randomly assigned either to a fixed group or a free group. The initial dosage was chosen according to the previous treatment history and then adjusted every two weeks following a predefined titration algorithm to meet the target mean fasting glucose levels (140 mg/dL). The medications were given for 16 weeks. The primary endpoint was the change in HbA1c level from baseline to week 16. Various parameters were checked as secondary outcome measures and safety criteria. RESULTS: HbA1c level of the fixed group and the free group decreased by 1.09% and 1.08%, respectively. The 95% CI of the changes' difference between the two groups (-0.21%, +0.19%) was within the predefined equivalence interval (-0.5%, +0.5%). Secondary outcome measures (the changes of fasting and postprandial plasma glucose level, response rate and compliance) and safety criteria (frequency of hypoglycemia and adverse reactions) were similar between the two groups. CONCLUSION: Fixed combination of glimepiride/metformin is as effective and safe therapy as free combination in type 2 diabetes patients.

Citations

Citations to this article as recorded by

Efficacy and safety of glimepiride/metformin sustained release once daily vs. glimepiride/metformin twice daily in patients with type 2 diabetes
Y.-C. Hwang, M. Kang, C. W. Ahn, J. S. Park, S. H. Baik, D. J. Chung, H. C. Jang, K.-A. Kim, I.-K. Lee, K. W. Min, M. Nam, T. S. Park, S. M. Son, Y.-A. Sung, J.-T. Woo, K. S. Park, M.-K. Lee
International Journal of Clinical Practice.2013; 67(3): 236. CrossRef
Pharmacokinetic comparison of a new glimepiride 1-mg + metformin 500-mg combination tablet formulation and a glimepiride 2-mg + metformin 500-mg combination tablet formulation: A single-dose, randomized, open-label, two-period, two-way crossover study in
Bo-Hyung Kim, Kwang-Hee Shin, JaeWoo Kim, Kyoung Soo Lim, Kyu-pyo Kim, Jung-Ryul Kim, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang, Kyung-Sang Yu
Clinical Therapeutics.2009; 31(11): 2755. CrossRef

Randomized, Open Label, Multicenter Clinical Trial about the Effect of Cilazapril on Vascular Endothelial Function in Patients with Type 2 Diabetes Combined with Hypertension.: Sang Youl Rhee, Jeong Taek Woo, Sei Hyun Baik, Hyoung Woo Lee, In Kyu Lee, Hye Soon Kim, Moon Kyu Lee, Min Ho Shong, Chung Gu Cho, Byoung Hyun Park, Bong Soo Cha, Young Seol Kim; Korean Diabetes J. 2006;30(6):450-458. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.450

2,283 View
21 Download
1 Crossref

Abstract PDF

BACKGROUND
The angiotensin converting enzyme inhibitor (ACEi) improves the vascular endothelial cell function and has a better clinical outcome by decreasing the LDL cholesterol oxidation, hypercoagulability, oxidative stress and improving the level of endothelial nitric oxide synthesis in patients with type 2 diabetes and hypertension. However, the correlations between the ACEi and the serum markers for the vascular endothelial function in previous studies were not consistent. SUBJECTS AND METHODS: Between July 2003 and April 2005, 104 type 2 diabetes patients with hypertension, who had been admitted to 9 major university hospitals in Korea, were examined. The subjects were randomly allocated to the cilazapril (2.5~5 mg/day) and atenolol (50~100 mg/day) treatment group and given a combination of hydrochlorothiazide and amlodipine. The lipid profile and the markers for endothelial function, such as vWF, VCAM, E-selectin, tPA, fibrinogen, adiponectin, hsCRP, nitrotyrosine were evaluated and the differences in the variables were compared with those obtained 6 months later. RESULTS: A total 56 subjects completed the 6-months follow up period. Regarding the baseline characteristics, there were no significant differences in the variables observed in the two groups except for HbA1c (P = 0.037), vWF (P = 0.048), and hsCRP (P = 0.038). After 6 months, both groups showed a significant and identical decrease in the systolic and diastolic blood pressure compared with the baseline (P < 0.002). However, there were no significant differences in the endothelial markers between each group. On the other hand, there was some deterioration in the triglyceride (P = 0.009) and HbA1c (P = 0.017) levels in the atenolol treatment groups. CONCLUSIONS: There were no significant differences in the endothelial function markers observed between the cilazapril and atenolol groups. However, cilazapril had an identical effect on the blood pressure reduction compared with atenolol but had fewer adverse effects on the glucose and lipid metabolism.

Citations

Citations to this article as recorded by

Potential Protective Role of Blood Pressure-Lowering Drugs on the Balance between Hemostasis and Fibrinolysis in Hypertensive Patients at Rest and During Exercise
Annabella Braschi
American Journal of Cardiovascular Drugs.2019; 19(2): 133. 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

1,984 View
20 Download

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.

Endoplasmic Reticulum (ER) Stress and Vascular Complication.: Hee Kyung Kim, In Kyu Lee; Korean Diabetes J. 2006;30(3):145-150. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.145

2,055 View
24 Download
2 Crossref

Abstract PDF

No Abstract available.

Citations

Citations to this article as recorded by

Binding of silver nanowaste using jellyfish immune reaction extract and an assessment of aquatic toxicity
Euna Kim, Min-Kyeong Yeo, Bong Gu Lee, Sun Woo Geum
Molecular & Cellular Toxicology.2022; 18(3): 339. CrossRef
Metformin Down-regulates TNF-α Secretion via Suppression of Scavenger Receptors in Macrophages
Bobae Hyun, Seulmee Shin, Aeri Lee, Sungwon Lee, Youngcheon Song, Nam-Joo Ha, Kyung-Hea Cho, Kyungjae Kim
Immune Network.2013; 13(4): 123. CrossRef

Alpha-Lipoic acid Inhibits TNF-alpha-Induced Fractalkine Expression in Rat aortic Smooth Muscle Cells.: Keun Gyu Park, Hye Soon Kim, Seong Yeol Ryu, Chang Wook Nam, Byung Kyu Chae, Eui Dal Jung, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2005;29(5):409-417. Published online September 1, 2005

1,043 View
24 Download

Abstract PDF: BACKGOUND: The induction of vascular inflammation via the proinflammatory cytokine/ nuclear factor (NF)-kappaB pathway is one of the key mechanisms in the development and progression of atherosclerosis. Accumulating evidence suggests a recently identified chemokine, fractalkine, is involved in arterial inflammation and atherogenesis; however, few studies have examined the effects of pharmacological agents on this process. The purposes of this study were to determine if alpha-lipoic acid (ALA) inhibits the expression of tumor necrosis factor (TNF)-alpha-stimulated fractalkine in vascular smooth muscle cells(VSMCs). METHODS: Rat VSMCs were isolated and cultured. Northern and Western blot analyses were performed to evaluate the effects of ALA on the expression of TNF-alpha-stimulated fractalkine in VSMCs. A gel shift assay was performed to examine the mechanism by which ALA inhibits the expression of fractalkine. RESULTS: TNF-alpha markedly induced the expression of fractalkine in primary cultured VSMCs. ALA inhibited the expression of TNF-alpha-stimulated fractalkine in cultured VSMCs. The result of the gel shift assay suggested the inhibitory effects of AS-6 on the expression of TNF-alpha-stimulated fractalkine were mediated via the NF-kappaB pathway. CONCLUSION: This study has shown that ALA has anti-inflammatory effects on VSMCs, which are mediated by the inhibitoin, at least in part, of the NF-kappaB dependent inflammatory signal-stimulated expression of fractalkine. Our data suggest the possibility that antioxidants, such as ALA, inhibit the NF-kappaB pathway, which may be used to prevent the development and progression of atherosclerosis.

Comparison of the Relationship of Leptin to Metabolic Parameters Between Premenopausal Normal Weight and Obese Women.: Hee Kyoung Kim, Keun Gyu Park, Mi Kyung Kim, Young Yun Jang, Sang Yoon Kim, Eui Dal Jung, Hye Soo Kim, Ju Ho Do, In Kyu Lee; Korean Diabetes J. 2005;29(3):223-230. Published online May 1, 2005

1,025 View
18 Download

Abstract PDF: BACKGROUND
Leptin is mainly secreted from adipose tissue, and it is a crucial factor for metabolic syndrome that is characterized by obesity, insulin resistance, hypertension and dyslipidemia. We measured the serum leptin concentrations and compared them with the body fat distribution and metabolic risk factors in premenopausal normal weight and obese women. METHODS: 231 premenopausal obese women participated in this study. The subjects were grouped based on their body mass index(BMI). The number of normal weight group women(BMI<25kg/m2) and the number of obese group women(BMI> or = 25kg/m2) were 90 and 141, respectively. We measured the plasma leptin concentration and such metabolic risk factors as fasting glucose, insulin, triglyceride(TG), systolic blood pressure(SBP) and diastolic blood pressure(DBP). The subcutaneous adipose tissue area(SAT) and the visceral adipose tissue area(VAT) were determined by computed tomography. The BMI, waist to hip ratio(WHR) and homeostasis model assessment(HOMA-IR) were calculated. RESULTS: In the obese group, the leptin levels were positively correlated with the BMI and SAT as well as with such metabolic risk factors as fasting serum glucose, insulin, HOMA-IR, TG, SBP and DBP. Although leptin levels were positively correlated with BMI and SAT in the normal weight group, they were not correlated with the metabolic risk factors. CONCLUSION: The present study showed that the leptin levels in the normal weight group were not associated with the metabolic risk factors. Therefore, the degree of obesity must be considered before leptin can be used as a predictor for metabolic syndrome including diabetes and coronary heart disease

Taurine-Mediated Restoration of Glucose Sensitivity of Pancreatic Beta Cells in OLETF Rats.: So Yeon Kim, Keun Gyu Park, In Kyu Lee, Seong Il Nam, Dae Kyu Song; Korean Diabetes J. 2005;29(3):198-205. Published online May 1, 2005

1,015 View
21 Download

Abstract PDF: BACKGROUND
An OLETF(Otsuka Long-Evans Tokushima Fatty) rat is a model of type 2 diabetes that is characterized by obesity-induced insulin resistance. Taurine has been known to be beneficial for type 2 diabetes. This study evaluated the potential taurine effect on the insulin response to high glucose in the islets of OLETF rats. METHODS: One percent of taurine was put in the drinking water for the taurine group of OLETF rats at the time of their being 20 to 39 weeks of age. At 40 weeks, the pancreatic islets and beta cells were obtained to measure the glucose-stimulated insulin secretion(GSIS) and the ATP-sensitive K+(KATP) channel current. RESULTS: Taurine supplementation had no effect on the weight change of the rats when this was measured weekly from 20 to 39 weeks(mean+/-SE: 702+/-19g in the control group vs. 688+/-18g in the taurine group at the 39th week). However, the GSIS was significantly potentiated in the taurine-treated rats(8.9+/-1.3% vs. 13.2+/-3.2% of the total secreted at 15 mM glucose for 1h). The glucose-induced KATP channel inhibition in the beta cells was also greater in the taurine group. CONCLUSION: Taurine supplementation is a beneficial tool for the restoration of GSIS in the pancreatic islet of the OLETF rats. Maintenance of blood taurine level may be important in treating type 2 diabetic patients, who are subject to a low blood level of taurine

Insulin Gene Therapy Using HVJ-liposome and Epstein-Barr Virus Plasmid in Murine Streptozotocin Induced Diabetes.: Yong Deuk Kim, Keun Gyu Park, Seong Wook Han, Jong Doek Ahn, Hyo Jung Lee, Mi Jung Kim, Hye Soon Kim, Nam Hee Park, In Kyu Lee; Korean Diabetes J. 2003;27(5):405-413. Published online October 1, 2003

1,163 View
22 Download

Abstract PDF: BACKGROUND
Despite improvement in insulin preparation and delivery, the use of insulin therapy alone to maintain normal glucose concentration and prevent the development of diabetic complication is not easy. Therefore, there has been considerable interest in developing gene therapy to supply insulin. We investigated that the administration of hemagglutinating virus of Japan (HVJ)- liposome complex, containing human insulin construct into the portal vein to control the blood glucose level in murine streptozotocin (STZ)-induced diabetes. METHODS: Human insulin gene was delivered to STZ-induced diabetic rats through the portal vein using HVJ-liposome containing Epstein-Barr virus (EBV) replicon-based plasmid (pEB). Blood glucose and body weight were measured after insulin gene delivery. The animals were sacrificed 28 days later and the livers were collected for immuno-histochemical staining of insulin. In addition plasma insulin and C-peptide levels were measured. RESULTS: Significant decrease in blood glucose levels and an increase in insulin and C-peptide levels were observed in the insulin gene transfection group as compared to the control group. Immunohistochemical staining of insulin also showed significant differences between these two groups. CONCLUSION: This study demonstrated the possibility of insulin gene therapy through the portal vein using pEB and HVJ-liposome method to produce a sustained improvement of diabetic glucose metabolism.

A Differential Effect of Intracellular ATP on Skeletal-and Smooth Muscle-Type KATP Channel Activities.: Oh Dae Kwon, Jeong Geun Lim, Haeng Gyun Kim, Dae Kwang Kim, Jae Seok Hwang, Keun Gyu Park, Sung Hee Park, Chi Heum Cho, In Kyu Lee, Dae Kyu Song; Korean Diabetes J. 2003;27(4):332-342. Published online August 1, 2003

917 View
18 Download

Abstract PDF: BACKGROUND
The ATP-sensitive potassium (KATP) channel comprises an inwardly- rectifying K+ channel (Kir) and a sulfonylurea receptor(SUR). This study investigated the mechanism of different ATP sensitivity between skeletal-(Kir6.2/SUR2A) and smooth muscle- (Kir6.2/SUR2B) type KATP channels. METHODS: Messenger RNAs encoding mouse Kir6.2, and rat SUR2A or 2B were co-injected into Xenopus Laevis oocytes to express each type of KATP channel. Using the inside-out patch clamp technique, the channel currents for MgATP sensitivity were measured and analyzed. RESULTS: By addition of 100 microM of MgATP, the current initially decreased and then slowly increased in Kir6.2/SUR2A. This gradual, ATP sensitivity decrease during prolonged MgATP application was totally blocked by LY 294002, a pho- sphatidylinositol-3 and -4 kinase inhibitor. In contrast, a rather rapid sensitivity decrease after initial inhibition was observed in Kir6.2/SUR2B by 100 microM of ATP, which was not blocked by LY 294002. This channel activation was Mg2+- dependent, suggesting that ATP hydrolysis is critical. CONCLUSION: This result supports the idea that the ability of MgATP to stimulate Kir6.2/SUR2B channels reflects a faster rate of ATP hydrolysis at NBD2 of SUR2B.

Effect and Mechanism of High Glucose Level on the Expression of an Adhesion Protein, beta ig-h3, and Cellular Function in Endothelial Cells.: Sung Woo Ha, Hye Jin Yeo, Jong Sup Bae, Sung Chang Chung, Jung Guk Kim, In San Kim, In Kyu Lee, Bo Wan Kim; Korean Diabetes J. 2003;27(4):323-331. Published online August 1, 2003

1,115 View
17 Download

Abstract PDF: BACKGROUND
Diabetes mellitus is a high risk condition for the development of atherosclerotic and thromboembolic macroangiopathy. There are many factors which are involved in development of these processes. Given the central pathogenic role of endotheliopathy in atherosclerosis, it is likely that this vascular monolayer is the ultimate target of injury in response to many cytokines and growth factors. A dysfunctional endothelium may contribute to the proatherogenic environment. Transforming growth factor (TGF-beta) is a key factor in the development of diabetic angiopathy and atherosclerosis because of its effect on the accumulation of extracellular matrix proteins and endothelial function. The adhesive molecule betaig-h3 is an extracellular matrix protein whose expression is induced by TGF-beta. Considering that TGF-beta plays an important role in diabetic complications and that betaig-h3 is a downstream target gene of TGF-beta, we hypothesized that betaig-h3 may also play a role in the development of diabetic angiopathy through its effect on the endothelial function. Therefore, we examined the effects of high glucose level on the expression of betaig-h3 and endothelial function in human umbilical vein endothelial cells (HUVECs). We also studied the mechanisms of this high glucose-induced betaig-h3 expression. METHODS: Endothelial cells were isolated from human umbilical cord and conditioned with different concentrations of TGF-beta or glucose. We measured TGF-beta and betaig-h3 protein presence/concentration/expression in cell supernatant by ELISA and examined whether TGF-beta is involved in high glucose-induced betaig-h3 expression. Finally, we investigated the biologic function of betaig-h3 in endothelial cells by using adhesion assay. RESULTS: Our study demonstrated that both high glucose level and TGF-beta induced betaig-h3 protein expression in HUVECs. High glucose level also induced TGF-beta protein expression in cells. Anti-TGF-beta antibody almost completely blocked high glucose-induced betaig-h3 expression. betaig-h3 was found to support the adhesion of endothelial cells. CONCLUSION: These results suggest that high glucose level upregulates betaig-h3 protein levels through the induction of TGF-beta and that betaig-h3 may play an important role in diabetic angiopathy by regulating adhesive function of endothelial cells.

Polymorphism of Melanocortin-4 Receptor and Obesity.: Hye Soon Kim, In Kyu Lee, Young Sung Suh; Korean Diabetes J. 2003;27(2):123-131. Published online April 1, 2003

905 View
27 Download

Abstract PDF: BACKGROUND
The application of genetics to obesity has made remarkable progress in recent years. The melanocortin-4 receptor (MC4R) regulates food intake, and possibly that of energy expenditure. The MC4R gene is the most prevalent obesity gene found to date in humans. The prevalence of single nucleotide substitution, replacing valine with isoleucine, at codon 103 was studied, and the role of the MC4R gene polymorphism on the body weight, fat distribution and lipid profile were determined. METHODS: Anthropometry and biochemical studies were performed on 226 subjects (82 male and 144 female subjects). The MC4R genotype was determined by a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. The body fat distributions were measured by computerized tomography. RESULTS: The frequencies of the homozygotes, Val103Val and Val103/Ile, were 88.9 and 11.1%, respectively. The frequencies of the heterozygotes were similar (11.8 vs. 10.6%) in the control and obese groups. However, the heterozygotes had lower waist-to-hip ratios (WHR) (p=0.033) and visceral fat masses (p=0.038) compared to the homozygotes. In the obese group, the heterozygotes had lower body mass indices (BMI) and visceral fat masses (p=0.043 and p=0.044, respectively). The heterozygote males had lower BMI and fasting plasma glucose levels (p=0.046 and p<0.001, respectively) than the homozygote males. The heterozygote females tended to have lower WHR (p=0.081) than the homozygote females. CONCLUSION: These results suggest that mutations in the MC4R gene are likely to be a cause of human obesity, and possibly of metabolic syndrome.

The Effect of alpha-lipoic Acid on Endothelial Dysfunction Induced by Intralipid Infusion in Healthy Volunteers.: Dong Wook Lee, Mi Jung Kim, Hye Soon Kim, Tae Sung Yun, Ho Chan Cho, Sang Jun Lee, Seung Ho Hur, Kyo Cheol Mun, Yong Won Cho, Jae Hoon Bae, In Kyu Lee; Korean Diabetes J. 2002;26(5):336-346. Published online October 1, 2002

2,779 View
24 Download

Abstract PDF: BACKGROUND
Endothelial dysfunciton has been proposed as an early manifestation of atherogenesis. Recently, emerging evidence suggests that hypertriglyceridemia and elevated free fatty acid are important risk factors in the development of atherosclerosis, probably through an increased oxidative stress. To clarify the hypothesis, we evaluated the effect of alpha-lipoic acid (ALA) on the endothelial dysfunction induced by intralipid infusion in healthy volunteers. METHODS: Hypertriglyceridemia and elevated free fatty acids was induced by infusion of intralipid. FMD (Flow-mediated dilation) of the brachial artery was investigated noninvasively by a high-resolution ultrasound technique in 13 young, healthy men without risk factors for coronary heart disease. RESULTS: Plasma triglyceride, free fatty acid and the superoxide anion were increased from 61.7+/-28.8 to 332.6+/-202.5 mg/dL, from 330.7+/-131.1 to 1267.0+/-486.2 microEq/L and from 6.6+/-2.2 to 8.7+/-1.5 X 10(-7)nmol/10(6)cells/30min (vs. basal p<0.001), respectively, following infusion of the intralipid. The FMD was decreased from 10.1+/-3.3 to 7.7+/-3.7% (vs. basal p<0.01) following infusion of the intralipid. After treatment with ALA, the increase in the FMD and the decrease in superoxide anion were significant. CONCLUSION: Acute hypertriglyceridemia, induced by intralipid infusion, is implicated in endothelial dysfunction. This endothelial dysfunction was reversed by treatment with ALA. These results suggest that chronic and repeated hypertriglyceridemia may play important roles in the development of atherosclerosis probably by increasing oxidative stress.

The Effect of Alpha-lipoic Acid on Endothelial Dysfunction in Postmenopausal Uncomplicated Type 2 Diabetes.: Ho Chan Cho, Sang Jun Lee, Mi Jung Kim, Hye Sun Kim, Tae Sung Yun, Sung Jae Kim, Sang Hyon Kim, Seung Ho Hur, Kyo Chul Moon, Jae Hoon Bae, In Kyu Lee; Korean Diabetes J. 2002;26(4):242-252. Published online August 1, 2002

1,470 View
20 Download

Abstract PDF: BACKGROUND
Recently, increased oxidative stress has been proposed as a major cause of vascular complications of patients with diabetes mellitus. Increased generation of oxygen free radicals in patients with diabetes mellitus could deplete cellular antioxidants and inactivate endothelial dependent vasodilating factor (EDRF), such as nitric oxide (NO). The purpose of this study was to evaluate whether the antioxidant alpha-lipoic acid (ALA) is effective in endothelial dysfunction of brachial artery, which induced by increased oxidative stress in postmenopausal diabetic women using high resolution ultrasound technique and initial reaction time (IRT) measurement. METHODS: We enrolled 11 menopausal women (mean age, 56.5+/-5.1 years) with uncomplicated type 2 diabetes. All patients were taking 1200 mg of ALA (Thioctacid(R), Bukwang, Korea). We measured of superoxide anion (O2-) in neutrophils as a marker of oxidative stress. Flow-mediated dilation (FMD) was measured using a high-resolution ultrasound. RESULTS: After treatment of ALA, fasting blood glucose was decreased significantly, the endothelium-dependent vasodilation of the brachial artery was increased, and O2- production was also decreased significantly. CONCLUSION: These results show that short term ALA treatment could improve the endothelial dysfunction in patients with type 2 diabetes mellitus. This improvement might be related with the antioxidants effect of ALA.

The effect of advanced glycation and products on the proliferation of vascular smooth muscle cell.: Hye Soon Kim, In Kyu Lee; Korean Diabetes J. 2002;26(2):87-90. Published online April 1, 2002

797 View
17 Download

Abstract PDF: No abstract available.

The Effects of Uncoupling Protein 3 Overexpression on Glucose Metabolism in OLETF Rats in Vivo and Cultured Skeletal Muscle Cells in Vitro.: Jeong Hee Han, Hye Seon Park, Jung Min Koh, Ha Young Kim, Ho Kyung Kang, In Kyu Lee, Joong Yeol Park, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee; Korean Diabetes J. 2001;25(6):460-468. Published online December 1, 2001

1,225 View
22 Download

Abstract PDF: BACKGROUND
UCP3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. METHODS: An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus- UCP3 (UCP3 group) and others were injected with the adenovirus (control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C12 cells transfected with ether an adenovirus or the adenovirus-UCP3. RESULTS: The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. CONCLUSION: Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism.

The Effect of alpha-Lipoic Acid on Vascular Smooth Muscle Cell Proliferation, Migration, Neointimal Formation and PAI-1 Expression.: Dong Woo Shin, Dong Wook Lee, Sang Jun Lee, Hye Soon Kim, Hyo Gyoung Kang, Jong Deok Ahn, In Kyu Lee; Korean Diabetes J. 2001;25(6):446-459. Published online December 1, 2001

1,179 View
24 Download

Abstract PDF: BACKGROUND
Exposure to large amounts of glucose causes a characteristic dysfunction and morphologic changes of the endothelium by an increased production of reactive oxygen species (ROS) in diabetes. The plasminogen activator inhibitor-1 (PAI-1), which modulates fibrinolysis and cell migration, may influence proteolysis and neointimal formation in vascular smooth muscle cells (VSMC). Antioxidants have been proposed to inhibit multiple proatherogenic events. This study investigated the effect of (alpha)-Lipoic acid on PAI-1 expression and VSMC proliferation and migration both in vivo and in vitro. METHODS: In the in vitro study, cultured rat aortic smooth muscle cells (RASMC) were incubated in a medium containing high glucose (22 mM) and 100 nM angiotensin II for 4 hour. After (alpha)-Lipoic acidtreatment, a -migration and growth assay of the RASMC, and a gel mobility shift assay and reporter gene analysis for nuclear factor- B (NF-kappa B) and northern blot analysis for PAI-1 were performed. In the in vivo study, the effect of (alpha)-Lipoic acid on neointimal hyperplasia in a rat carotid balloon injury model was evaluated. RESULTS: RASMC migration was inhibited significantly by (alpha)-Lipoic acid (p<0.01), but their proliferation was not inhibited. The NF-kappa B DNA binding activity and NF-kappa B promoter activity was inhibited by (alpha)-Lipoic acid significantly (p<0.01). (alpha)-Lipoic acid inhibited PAI-1 mRNA expression by high glucose and angiotensin II in dose dependent manner (p<0.05). In the rat carotid artery balloon injury model, neointimal formation was reduced by (alpha)-Lipoic acid treatment in a dose dependent manner significantly (p<0.01). CONCLUSION: (alpha)-Lipoic acid suppresses migration, but not proliferation in RASMC. (alpha)-Lipoic acid also reduce neointima formation in a rat carotid balloon injured model. This effect might be related to the blocking of NF-kappa B which increase the expression of the genes associated with atherosclerosis including TNF-alpha, IL-1, IL-6, endothelin-1, MCP-1, VCAM-1, ICAM-1, E-selectin, tissue factor.

Evaluation of Vascular Endothelial Function.: In Kyu Lee; Korean Diabetes J. 2001;25(6):406-423. Published online December 1, 2001

845 View
17 Download

Abstract PDF: No abstract available.

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

1,422 View
27 Download

Abstract 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.

The Effect of Acute Hyperglycemia on Endothelial Function in Type 2 Diabetes.: Sang Jun Lee, Dong Wook Lee, In Kyu Lee; Korean Diabetes J. 2000;24(5):574-586. Published online January 1, 2001

1,065 View
16 Download

Abstract: BACKGROUND
Multiple studies in patients with diabetes demonstrate impaired endothelial-dependent vasodilation. But the mechanisms of vascular dysfunction in type 2 diabetes are still controversial. Some risk factors, such as dyslipidemia, hypertension and obesity, are commonly associated with type 2 diabetes. These risk factor may cause endothelial dysfunction. And hyperglycemia may have a specific role in the increased risk of vascular complications in diabetes but it remains unclear. The purpose of this study was to examine whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading. METHOD: Using the high-resolution ultrasound, we measured flow-mediated vasodilation (endothelial dependent vasodilation: FMD) during oral glucose tolerance test in 11 men (mean age: 59+/-5 years) with type 2 diabetes without chronic diabetic complications. For statistical analysis, we used paired t-test, generalized linear method (GLM) to compare FMD before and after glucose loading. RESULT: Flow-mediated vasodilation was diminished after glucose loading (13.2+/- 6.4%, 7.3+/-3.3*%, 12.8+/-5.6%, in fasting, at 1- and 2-h, respectively; *p<0.001 vs fasting). Superoxide anion formation by neutrophils was increased after glucose loading (4.65+/-2.8, 6.17+/-2.2, in fasting, at 1-h respectively: p<0.05 vs fasting)( 10-7nmol/106cells/30min). Endothelial independent vasodilation was not significantly affected by glucose loading. The concentration of triglyceride were not changed after glucose loading. CONCLUSION: This study shows that acute hyperglycemia induced by 75 gm oral glucose intake results in endothelial dysfunction. These results suggest that prolonged and repeated hyperglycemia may play an important role in the developement and progression of vascular complication in diabetes.

An Effect of Estrogen Supplementation on the Endothelium Dependent Vasodilation in Postmenopausal Women with Type 2 Diabetes Mellitus.: Jun Kim Yeo, Sang Jun Lee, In Kyu Lee; Korean Diabetes J. 2000;24(1):37-45. Published online January 1, 2001

1,097 View
17 Download

Abstract PDF: BACKGROUND
Although estrogen supplementation can reduce cardiovascular events in postmenopausal women, but the mechanism that mediate this beneficial effect is unclear. Thus, we investigated the acute effect of HRT on endothelial dependent vasodilation using high resolution ultrasound in healthy and diabetic postmenopausal women. METHOD: We examined endogenous (flow dependent dilatation affer 5min cuff occlusion) and exogenous (sublingual nitroglycerin) nitric oxide mediated vasodilation in the brachial artery before and after estrogen supplementation (Premarin R 0.625 mg for 1 wk) in 16 postmenopausal women, and in 18 age-matched postmenopausal women with type 2 diabetes mellitus. RESULTS: There were no differences in age, total & LDL cholesterol level, and body mass index between the groups (p>0.05). However, HDL cholesterol level was significantly lower in patient with diabetes than in normal women (1.0+/-0.3 mmol/L in diabetes and 1.4+/-0.2 mmol/L in normal, p<0.05). Basal endothelium dependent vascular reactivity was significantly attenuated in patient with diabetes when compaired with normal subjects (8.0+/-3,9% versus 13.7+/-6.2%, p<0.05). An estrogen supplementation increased endothelium dependent vasodilation not only in patient with diabetes(from 8.0+/-3.9% to 15.1+/-4.0%, p<0.05), but also in normal women (from 13.7+/-6.2% to 20.1+/-4.7%, p<0.05). Moreover the percent increase of vascular reactivity was higher in patient with diabetes(p<0,05), In contrast, the responses to sublingual nitroglycerin were comparable in diabetes (from 21.1+/-6.0% to 22.1+/-4.1%, p>0.05), and in normal women (from 25.8+/-7.8% to 25.2+/-4.5%, p>0.05) before and after estrogen supplementation. CONCLUSION: Endothelial dysfunction was prominent in patient with diabetes and it was significantly attenuated by estrogen. These results suggest that estrogen replacement improves endothelial dependent vasodilation in healthy and diabetic postmenopausal women.

Mesurement of GAD Antibodies using Radioligand Binding Assay, IRMA and RIA in Patients with Tye 1 Diabetes Mellitus.: In Kyu Lee, Hyoung Woo Lee, Kyu Chang Won, Hyun Dae Yoon, In Ho Cho, Ji Sung Yoon, Sang Yiup Nam, Jung Hyun Oh, Jin Cheol Park, Jae Hong Kim; Korean Diabetes J. 1999;23(3):278-287. Published online January 1, 2001

1,257 View
20 Download

Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include insulin autoantibodies (IAAs), cytoplasmic islet cell antibodies (ICA) and GAD antibodies. Recently, there has been increasing interest in the use of glutamic acid decarboxylase antibodies (GADA) for the identification of subjects with increased risk of developing type 1 diabetes. GAD antibodies were first discovered in 1982 and is detected persistently after long duration of type 1 diabetes, whereas ICA is transient. However, because the classic immunoprecipitation assays of GAD antibodies is still rather time-consuming, a more simple and reproducible radiolignad binding assay (RBA) is has been widely used recently. The RIA (radioimmunoassay) and IRMA (immunoradiome- tricassay) for GAD antibodies using (125)I-labelled human GAD has been developed, The aim of the present study is to evaluate the usefulness of each methods. METHODS: We measured GAD antibodies by RBA with in vitro spathesized recombinani S-methio- nine-labelled GAD65, and protein A-sepharose to separate free from antibody-bound ligand and radioimmunoassay and immunoradiometric assay using 'I-labelled human GAD kit, in addition to measurement of ICAs by standard indirect immunofluorescence technique in 26 patients with type 1 diabetes(male 10, female 16, mean age 14 years) and 10 normal controls(male 5, female 5, mean age 15 years). RESULTS: The overall prevalence of GAD antibodies by RBA and RIA in patients with type 1 diabetes was 38% (10/26), respectively. The prevalence of GAD antibodies by IRMA in patients with type 1 diabetes was 31% (8/26). The frequency of GAD antibodies by RBA,IRMA and RIA increased as the JDF unit of ICA increased. There is a significant correlation between the GAD index (by RBA) and GAD concentration (by RIAand IRMA). CONCLUSION: These results suggest that GAD antibodies (by RIA or RBA or IRMA) is useful for screening and diagnosis of type 1 diabetes in Korean, but long-term prospective studies on large cohorts of patients is necessary.

Plasma Concentrations of Plasminogen Activator Inhibitor-1(PAI-1) and Lipoprotein(a) in Non-Insulin-Dependent Diabetes Mellitus with Peripheral Vascular Disease.: Sung Jin Nam, Sung Rae Cho, Choo Sung Kim, Sang Gyun Woo, Hee Jin Choi, Sang Ki Kim, Jae Hong Park, In Kyu Lee, Seong Bum Han, Seung Yup Han, Chung Chul Kim; Korean Diabetes J. 1999;23(1):55-61. Published online January 1, 2001

1,196 View
20 Download

Abstract PDF: OBJECTIVES
The plasminogen activator inhibitor-1 (PAI-I) and lipoprotein(a) are considered as important fibrinolysis inhibitors. We evaluated PAI-1 and Lp(a) concentrations in Korean non-insulin- dependent diabetes mellitus (NIDDM) patients with or without peripheral vascular disorder. METHODS: By using National Diabetes Data Group (NDDG) criteria as a diabetes mellitus diagnostic criteria, a total of 127 Korean NIDDM patients were seleeted. The ankle brachial index was measured by segrnental volume plethysmography to diagnose peripheral vascular disease. We also examined clinical and biochemical parameters in NIDDM patients. RESULTS: The duration of diabetes, systolic and diastolic pressures was significantly higher in diabetic patients with peripheral vascular disease (Group 2) than in diabetic patients without peripheal vascular disease (Group 1). The 24 hour urine microalbumin and PAI-1 levels in Group 2 were also significantly higher and the HDL-cholesterol level was lower than in Group 1. There were significant correlations between the plasma level of PAI-1 and BMI (r=0.466, p=0,007) or C-peptide level(r=0.517, p=0.012). Multivariate logistic regression analysis showed that Lp(a) and PAI-1 are independent risk factors for peripheral vascular disease. CONCLUSION: In the light of these results, it seems reasonable to suggest that high levels of PAI-1 and Lp(a) in NlDDM patients may play a role in the pathogenesis of peripheral vascular disease.

Upregulation of Aldose Reductase mRNA by Hyperglycemia in Claf Pulmonary Artery Endothelial Cells.: Sang Yiup Nam, Jung Hyun Oh, Jin Chul Park, Ji Sung Yoon, Kyu Chang Won, Chan Woo Lee, Ihn Ho Cho, Choong Ki Lee, In Kyu Lee, Hyoung Woo Lee; Korean Diabetes J. 1998;22(3):290-298. Published online January 1, 2001

1,373 View
19 Download

Abstract PDF: BACKGROUND
Hyperglycemia is thought to be an important etiologic factor in the development of diabetic macro- and microangiopathies. Several theories have been proposed to explain why diabetic patients are at an increased risk for such vascular disorders. In uncontrolled diabetes, excess glucose causes a glycation of various proteins, an increase in oxidative stress, an increase in DAG or PKC and an increase in polyol pathway. And, it has been proposed that hyperglycemia leads to the dysfunction or damage of endothelial cells through the activation of cellular aldose reductase(polyol pathway). METHODS: To verify this hypothesis, we quantitated AR(Aldose reductase) activity and mRNA in CPAE(Calf pulmonary artery endothelial) cell under normal and high ambient glucose levels in the culture medium. The time course of AR mRNA expression after exposure of CPAE cells to 22mM glucose was determined using PCR quantitative analysis. RESULTS: AR mRNA levels began to increase at 6h after glucose exposure, reached a maximum at 24h (about 2.3 fold increase), and then gradually decreased. Aldose reductase activity was found to strongly correlate with aldose reductase mRNA expression after cells were exposed to 22mM glucose. In contrast, aldose reductase mRNA expression at 24h after glucose exposure decreased following exposure to 50mM glucose. By testing other osmolytes, we also examined whether the AR activity is specific for glucose. There was an increase in AR activity only after the addition of 20mM mannitol to the medium. CONCLUSION: These observations suggest that hyperglycemia could induce the overexpression of aldose reductase mRNA in cultured CPAE cells and this could be an important step in the pathogenesis of diabetic complications.

Modecular Approach in Vascular Disease.: In Kyu Lee; Korean Diabetes J. 1997;21(2):122-126. Published online January 1, 2001

676 View
17 Download

Abstract PDF: No abstract available.

Effects of insulin and insulin-like growth factor-1 on collagen and fibronectin synthesis in endothelial cells and fibroblasts.: In Kyu Lee, Byung Chae Jo, Kun Young Sohn, Rang Woon Park, In San Kim; Korean Diabetes J. 1993;17(4):351-358. Published online January 1, 2001

773 View
17 Download

Abstract PDF: No abstract available.

Effects of oral glucose ingestion on plasma amylin concentration in diabetic and nondiabetic humans.: In Kyu Lee, Keun Yong Park, Hyoung Woo Lee; Korean Diabetes J. 1993;17(3):259-265. Published online January 1, 2001

840 View
20 Download

Abstract PDF: No abstract available.

Author index