- Role of Glucocorticoid Receptor on Insulin Secretion and Synthesis in INS-1 Cells.
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Ju Yeon Yang, Myong Su Kang, Tak Ho Song, In Kook Jeong, Pyong Ju Seo, Hee Jin Kim
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Korean Diabetes J. 2006;30(6):428-434. Published online November 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.6.428
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 Abstract
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- BACKGROUND
Glucocorticoids play important roles in the regulation of glucose homeostasis. It is well known that glucocorticoids reduce hepatic and peripheral tissue sensitivity to insulin, but the roles of glucocorticoids on insulin secretion and synthesis in pancreatic beta cells are still unclear. We have investigated the direct effects of glucocorticoids on insulin secretion and synthesis in rat insulinoma (INS-1) cells. METHODS: Insulin content and 11.2 mM glucose-stimulated insulin secretion (GSIS) were measured in INS-1 cells after culture with or without 1 micrometer dexamethasone (DEX). Preproinsulin mRNA levels were analyzed by real-time RT-PCR and normalized to the internal control. Effect of RU486 on DEX-induced inhibition of GSIS and preproinsulin mRNA synthesis was evaluated. RESULTS: Insulin content of INS-1 cells cultured in RPMI containing 11.2 mM glucose in the presence of DEX was not different from that of control cells. After 1-h preincubation in 2.8 mM glucose, basal insulin secretion from cells treated with DEX did not differ from that of controls, but GSIS was significantly reduced in the cells treated with DEX in comparison to control cells. The expression of preproinsulin mRNA relative to beta-actin mRNA was also lower in the cells treated with DEX. Glucocorticoid receptor antagonist improved DEX-induced inhibition of GSIS and preproinsulin mRNA synthesis. CONCLUSION: DEX inhibited GSIS and preproinsulin mRNA synthesis in INS-1 cells. Glucocorticoid receptor antagonist ameliorated the reduced GSIS and preproinsulin mRNA synthesis induced by DEX.
- Prevalence of Islet Cell Autoantibodies and Mitochondrial DNA Mutation among Typical and Atypical Type 1 Diabetic Patients in Korea.
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Hong kyu Lee, Kee Up Lee, Sung Kwan Hong, Byuong Doo Rhee, Dong Seop Choi, Hyoung Woo Lee, Sang Wook Kim, Hee Jin Kim, Nan Hee Kim, Kyong Soo Park, Woo Je Lee, Kyung Soo Ko
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Korean Diabetes J. 1999;23(4):541-551. Published online January 1, 2001
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Abstract
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- BACKGROUND
American Diabetes Association (ADA) proposed new criteria for the classification of diabetic patients, which were mainly based on the presence of autoimmune markers. But it is questionable if we can apply the new ADA criteria to Korean type 1 diabetic patients directly. In this study, we measured several autoantibodies to islet cell in Korean subjects with typical and atypical clinical manifestations of type 1 diabetes mellitus. And mutation of mitochondrial DNA was analyzed in the same patients. METHODS: We measured fasting serum C-peptide in 1870 diabetic patients attending the diabetes clinic of Asan Medical Center. Among the 117 patients with fasting serum C-peptide less than 0.6 ng/mL, glucagon-stimulated C-peptide was measured, and 57 Patients showed the level less than 1 ng/mL and they were diagnosed as type 1 diabetic patients. They were subgrouped into typical (n=26, needed insulin injection within 1 year after diagnosis) and atypical (n=30, did not need insulin for more than l year after diagnosis) type 1 diabetic patients. ICA was measured by indirect immunofluorescence method. Anti-GAD antibody was measured by radioimmunoassay. Anti-ICA512 antibody was measured by western blotting. Mitochondrial DNA 3243 mutation was detected using restriction enzyme Apa-I digestion of the amplified genomic DNA from the subjects. RESULTS: 1) Median age of onset was 40 years for atypical type 1 diabetes patients, while it was 27.5 years for typical type 1 diabetes patients. Average duration of insulin requirement was 0.18 years for typical group and 5.73 years for atypical group. In this series, only typical type 1 diabetic patients experienced diabetic ketoacidosis. 2) Only 50 % of typical type 1 diabetic patients and 47 % of atypical type 1 diabetic patients had at least one autoantibody among ICA, anti-GAD antibody and anti-ICA512 antibody. 3) Mitochondrial DNA 3243 point mutation was detected in 3 patients with atypical type 1 diabetes (10 %), but it was not found in patients with typical type 1 diabetes. CONCLUSION: These results suggest that the prevalence of autoantibodies in Korean type 1 diabetic patients was lower than that reported in Caucasians irrespective of clinical features. Therefore, it may not be easy to apply this new diabetes classification of ADA to Korean type 1 diabetic patients. In addition, mitochondrial DNA mutation may be responsible for some of the Korean atypical type 1 diabetic patients.
- A Study on the Patterns of Clinical Characteristics according to Body Weight and Weight Changes in Korean NIDDM Patients.
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Young Sun Hong, Hee Jin Kim, Yeon Ah Sung, Nan Ho Kyung
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Korean Diabetes J. 1997;21(1):65-73. Published online January 1, 2001
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Abstract
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- BACKGROUND
It is known that Korean NIDDM patients are mainly non-obese and have experienced weight loss frequently during the course of the disease. However, there have been few studies about the patterns of treatment and complications according to the weight changes, Our purpose was to determine the characreristics of diabetes in Korea by examining the differences in the clinical features according to the current weight and the weight changes. METHODS: From 308 Korean NIDDM patients. We obtained the data about the weight at the time of maximal obesity and diagnosis of diabetes and measured the current weight and height. We also evaluared the presence of diabetic retinopathy, nephropathy and neuropathy, We designated the patients with BMI 21kg/m and less as the lean group, the patients with BMI 21 to <26kg/m as the middle-range group and the patients with 26kg/m and over as the obese group. RESULTS: At the time of maximal weight, 61.4% of the patients were obese, but 40.3% were obese at diagnosis and only 33.8% were obese at recruitment. In the lean group, C-peptide was low and the frequency of insulin therapy was high. Although there was no statistical significance, diabetic complications were more frequent in the lean group. The percentage of the patients who lost weight (loss of 10% trom the maximal weight) was 65.9% in the lean group, 42.3% in the middle-range group and 32.7% in the obese group. The prevalence of retinopathy and neuropathy were higher in the group with weight loss, although not significantly. CONCLUSION: Of 308 NIDDM patients, 42.2% experienced weight loss before and after the diagnosis and only 33.8% were obese at recruitment. In the lean group, insulin secretory capacity was low and the frequency of insulin therapy was high. Our study showed that the lean group and the patients who have lost weight tended to have higher prevalence of the complications. The mass prospective study about the clinical characteristics according to weight changes in Korean NIDDM patients would be needed.
- Significance of Serum Anticardiolipin Antibody in Non-Insulin Dependent Diabetes Mellitus.
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Hee Jin Kim, Young Sun Hong, Yeon Ah Sung, Nan Ho Kyung
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Korean Diabetes J. 1997;21(1):39-48. Published online January 1, 2001
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Abstract
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- BACKGROUND
The antiphospholipid antibodies have been characteristically found in the patients with autoimmune diseases. Some previous studies revealed that antiphospholipid antibodies are increased in the sera of patients with diabetes and correlate with the extent of neuropathy and measurements of amiphospholipid antibodies may constitute a marker for ongoing damage to nerves. We measured serum anticardiolipin antibodies(IgG, IgM) to assess the prevalence and significance of anticardiolipin antibodies in NIDDM patients. METHOD: Ninety NIDDM patients were screened for lgG/IgM isotypes of anticardiolipin antibodies by enzyme-linked immunosorbent assay and compared with 30 control subjects. RESULTS: 1) The titers and positivities of IgG anticardiolipin antibodies were significantly higher in the sera of NIDDM patients than those of control subjects(P<0.05). 2) In NIDDM patients with IgG anticardiolipin antibody, the titer of serum c-peptide was significantly lower(P<0.05) and the body mass index tended to be lower(P=0.08). 3) There were no significant differences of positivities of IgG anticardiolipin antibodies according to the state of chronic diabetic complications and the mode of treatment(P>0.05). 4) In the patients with NIDDM, no significant association was found between the titers of IgG anticardiolipin antibodies and age, diabetic duration, fasting blood glucose, HbAlc, total cholesterol and triglyceride. CONCLUSION: The titers and positivities of IgG anticardiolipin antibodies were elevated in NIDDM. In the NIDDM patients with IgG anticardiolipin antibody, the serum titers of c-peptide were significantly lower and the body mass index tended to be lower. It seems that serum IgG anticardiolipin antibodies might have autoimmune relationship with slowly progressive IDDM, but further prospective mass studies will be requird.
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