- Effective Glycemic Control Achieved by the Transplantation of VEGF-Transfected Islets in STZ-induced Diabetic Mice.
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Byung Wan Lee, Hee Young Chae, You Ran Ahn, Seung Hoon Oh, Ji Youn Kim, Yun Jae Chung, Sang Young Kim, Kyun Yung Cho, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2005;29(4):282-294. Published online July 1, 2005
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 Abstract
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- BACKGROUND
Hypoxic damage is one of the major causes of early islet graft failure, and VEGF is known to play a crucial role in revascularization. We tried to evaluate whether the VEGF transgene in an islet graft can increase islet revascularization and; therefore, increase the survival rate of transplanted islets in order to achieve effective glycemic control in diabetic mice models using a non-viral cationic lipid reagent for gene delivery into non- dividing islet cells. METHODS: Human VEGF165 cDNA was transfected into Balb/c mice islets using Effectene, and the vascular neogenesis and glucose levels examined in the recipient syngeneic Balb/c mice. A minimal number of VEGF-transfected islets(100 IEQ/animal) were transplanted into STZ-induced diabetic mice. The recipient mice were classified into three groups: islet transplantation(IT) without intervention(IT-alone group, n=8), IT with an islets transduced rhoJDK-control vector(IT-rhoJDK group, n=8), and IT with an islets transduced rhoJDK-VEGF vector(IT-rhoJDK-VEGF group, n=8). RESULTS: The transfection efficiency was highest with 4microgram/microliter cDNA and 25microliter Effectene(1: 6 weight ratio), with satisfactory cell viability under these conditions. The overproductions of VEGF mRNA and proteins from the conditioned cells were confirmed. A minimal number of the VEGF-transfected islets(100 IEQ/animal) were transplanted into STZ-induced diabetic mice. The control of hyperglycemia in the IT-alone(0/8) and IT-rhoJDK groups(0/8) failed. However, complete abrogation of hyperglycemia and viable islets, and an increased vascularization of the VEGF-transfected grafts were identified in the renal capsules of the IT-rhoJDK-VEGF group(8/8). CONCLUSION: These studies support the utility of VEGF-transfected islet delivery using a cationic lipid reagent to achieve euglycemia with minimal islets via neovascularization.
- The Effects of Troglitazone on Vascular Smooth Muscle Cell Proliferation.
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Yun Jae Chung, Kyeong Min Min, Eun Young Oh, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2000;24(3):348-355. Published online January 1, 2001
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Abstract
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- BACKGROUND
Elevated fasting and postprandial insulin levels are frequently observed in patients with obesity and hypertension as well as type 2 diabetes mellitus. This phenomenon has been suggested as an independent risk factors for atherosclerotic cardiovascular diseases. Troglitazone, an insulin-sensitizing antidiabetic agent, has been shown to inhibit atherosclerotic process, but its mechanism of action is not yet elucidated. This study was undertaken to examine the effects of troglitazone, a peroxisome proliferator- activated receptor- (PPAR ) ligand, on vascular smooth muscle cell proliferation. METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats and the effects of several different agonists (insulin, ET-I, IGF-I) on cellular DNA synthesis were measured and compared with the effects of troglitazone. In addition, the mRNA of PPARgamma gene in rat aortic smooth muscle cells(RASMCs) was detected by RT-PCR methods. RESULTS:1. Insulin, endothelin-I and IGF-I significantly stimulated DNA synthesis in RASMCs (p<0.05). 2. Insulin-induced DNA synthesis was not significantly inhibited by coincubation with wortmannin or LY294002 but inhibited by PD98059. 3. Troglitazone significantly inhibited insulin, endothelin-I and IGF-I-induced DNA synthesis in RASMCs (p<0.05, respectively). 4. PPAR mRNA was detected in RASMCs by RT-PCR and its expression did not significantly increase by troglitazone treatment. CONCLUSION: Troglitazone could inhibit agonist-induced proliferation of vascular smooth muscle cells and might be a useful agent for treatment as well as prevention of atherosclerosis.
- The Appropriteness of New ADA Diagnostin Criteria for Diabetes Mellitus in Korean Population.
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Moon kyu Lee, Myung Shik Lee, Young Ki Min, Sung Hoon Kim, Byoung Joon Kim, Dong Jun Kim, Jong Ryeal Hahm, Eun Young Oh, Yun Jae Chung, Kyoung Ah Kim, Jae Hoon Chung, Kwang Won Kim
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Korean Diabetes J. 1999;23(3):336-351. Published online January 1, 2001
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Abstract
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- BACKGROUND
The ADA has proposed a new diagnostic criteria for diabetes based on fasting plasma glucose, redefining diabetes as fasting plasma glucose 7.0 mmol/L. Since only a few studies for the appropriateness of tbis new ADA criteria were undertaken in the Korean population, we examined the appropriateness of the new ADA criteria by analyzing the results of oral glucose tolerance tests done in our hospital. METHODS: 507 oral glucose tolerance tests were conducted. Cases with diabetes and diseases that could affect the glucose tolerance were excluded. Plasma glucose was measured by the hexokinase method. Three groups of NGT, IGT, and DM by the WHO criteria of 2 hour-plasma glucose were redivided at each level of fasting plasma glucose. We calculated the sensitivity and specificity of each level of fasting plasma glucose (FPG), and the FPG value of maximum accuracy to diagnose diabetes with reference to the WHO criteria of 2 hour-plasma glucose. RESULTS: Correlation between the levels of fasting plasma glucose and 2 hour-plasma glucose was relatively low (r=0.676). FPG of 7.0 mmol/L for diagnosing diabetes was relatively specific (specificity=0.934), but not sensitive (sensitivity= 0.552). FPG value of maximum accuracy for diagnosing diabetes was 6.8 mmol/L. 39 % of IFG (> 6.1mmol/L and < 7.0mmol/L) was reclassified as diabetes by the criteria of 2 hour plasma glucose 11.1 mmol/L and 34 % of NFG (<6.1mmol/L) was reclassified as impaired glucose tolerance by the criteria of 2 hour plasma glucose > 7.8 mmol/L. CONCLUSION: The fasting plasma glucose of 7.0 mmol/L was relatively specific for diagnosing diabetes. However, the new ADA criteria tended to underestimate the prevalence of diabetes and impaired glucose tolerance in the Korean population. Therefore, oral glucose tolerance test may be needed to diagnose diabetes in high risk subjects. Large-scale cross-sectional and prospective studies will be needed to clarify these points.
- Plasma leptin Concentrations in Korean Type 2 Diabetic Patients.
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Eun Young Oh, Yun Jae Chung, Yoon Ho Choi, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 1998;22(4):531-537. Published online January 1, 2001
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Abstract
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Obesity is a well-established risk factor for a number of chronic diseases, including type 2 diabetes mellitus, hypertension, cardiovascular disease, and hyperlipidemia. Leptin, the protein procluct of the ob gene, is increased in obese individuals, suggesting resistance to its effect. We investigated whether the subjects with type 2 diabetes have an altered regulation of serum leptin levels METHODS: 205 Korean type 2 diabetic patients and 174 normal contro1 subjects participated in this study. We evaluated a difference between leptin level of diabetic patients and that of normal controls. In diabetic patients, correlations among plasma leptin concentration and other factors such as serum insulin concentration, percentage body fat, BMI, gender, total cholesterol, triglyceride, and fasting serum glucose level were evaluated. RESULTS: Fasting plasma leptin concentrations were correlated to BMI, percentage body fat, gender and serum insulin concentration. Plasma leptin concentrations are not significantly different in diabetic subjects compared to controls. CONCLUSIONS: We conclude that there was no significant difference in semm leptin level between type 2 diabetic and normal subjects and that body fat, sex, and the fasting insulin level are independently associated with plasma leptin level in type 2 diabetic patients.
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