- The Changes in Insulin Secretion and GTPase Activity after the Exposure to High Glucose in Rat Pancreatic Islets.
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Young Sun Hong, Yeon Ah Sung, Nan Ho Kyung
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Korean Diabetes J. 2000;24(5):515-523. Published online January 1, 2001
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 Abstract
- BACKGROUND
Type 2 diabetes mellitus is characterized by defective glucose- induced and glucose-potentiated insulin secretion. Chronic elevation of glucose levels are considered to be a cause of impaired insulin secretion. It has been suggested that such defects in insulin secretion can be related to the alteration in stimulus-secretion coupling. Recent studies have provided evidences for the existence of guanine nucleotide-binding protein (G protein), and the regulatory role of G protein and GTPase activity in stimulus-secretion coupling in pancreatic islets. This study was performed to determine whether the exposure to high glucose concentration alters GTPase activity with decreased insulin secretion in pancreatic islets isolated from normal rats. METHODS: Pancreatic islets isolated from normal Sprague-Dawley rats were incubated in high (20 mM) and low (5 mM) glucose concentration for 48 hours. After incubation, glucose (20 mM) induced insulin secretion was measured. Then subcellular fractions of islets by homogenization and differential centrifugation were obtained and glucose induced inhibition of GTPase activities in each fraction was measured. RESULTS: 1) After 48 hour exposure to 5 mM and 20 mM glucose, insulin secretion in response to 20 mM glucose were 134.4+/-16.8 fmol/10 islets/hr and 90.0+/-10.2 fmol/10 islets/hr, respectively. After the exposure to high glucose, glucose-induced insulin secretion significantly decreased (p<0.05). 2) In each subcellular fraction, there was no significant difference between the islets exposed to 5 mM and 20 mM glucose in the degree of inhibition of GTPase activities by high glucose. CONCLUSION: The exposure to high glucose for 48 hours decreased insulin secretion without any significant differences in the degree of inhibition of GTPase activities. This results suggest that impaired insulin secretion by high glucose is not associated with the change in GTPase activity.
- Relation of Angiotensin Converting Enzyme (ACE) Gene Polymorphism to Insulin Sensitivity and Carotid Atherosclerosis in Female Nondiabetic Offspring of NIDDM Patients.
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Jee Young Oh, Yeon Ah Sung, Nan Ho Kyung, Yeon Jin Jang
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Korean Diabetes J. 1999;23(6):831-842. Published online January 1, 2001
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- BACKGROUND
Angiotensin converting enzyme (ACE) gene polymorphism has been known to related to atherosclerotic heart disease such as acute myocardial infarction or left ventricular hypertrophy, diabetic nephropathy or retinopathy, as well as, insulin sensitivity. However, an exact relationship between ACE gene polymorphism and aforementioned diseases have not been fully established. It has been suggested that NIDDM and atherosclerosis may have common pathogenesis since some of NIDDM patients already have atherosclerotic changes at the time of the initial diagnosis. Futhermore, offspring of NIDDM patients are considered as a high risk group for both NIDDM and atherosclerosis, and these two disorders are known to be affected by some common genetic factors. Therefore, in the present study, we planned to investigate, by analyzing female offspring of NIDDM patients (offspring), the relationship of ACE gene polymorphism to insulin resistance and atherosclerosis. METHODS: Fifty-three female offspring of patients with NIDDM were participated in this study, and twenty age-BMI matched normal glucose tolerant subjects without a family history of diabetes were selected as the controls. Based on 75-g oral glucose tolerance test, subjects were divided into normal glucose tolerance (n=42) or impaired glucose tolerance (n=ll). We assessed the patterns of body fat distribution by anthropometric measurement, bioelectric impedence analysis and computed tomogram; insulin sensitivity by minimal model analysis using insulin modified frequently sampled intravenous glucose tolerance test; carotid intima-medial thickness by ultrasonography. We investigated the alleles of the ACE gene by PCR. RESULT: 1. ACE genotypes in offspring were distributed as follows; 39.6% for II, 32.0% for ID, 28.4% for DD 55.7% for I al#lele, 44.3% for D allele. This distribution was not significantly different from those in controls (35.0% for II, 55.0% for ID, 10.0% for DD, 62.5% for I allele, and 37.5% for D allele). 2. There was no significant difference in body mass index (BMI), systolic and diastolic blood pressure, and serum lipid concentrations among three genotypes. However, in the subjects with ID genotype, VSR was significantly increased compared to the subjects with DD genotype (p<0.05). In the subjects with ID genotype, percent body fat, visceral fat area, CIMT were increased, and SI and SG were decreased in comparison to II and DD subjects, although the differences between the two groups did not reached the statistical significance. 3. When the subjects were divided into quartiles of CIMT, the frequency of ID genotype of ACE showed the tendency of increment from the lowest to the highest quartile of CIMT. 4. Multiple regression analysis showed that ACE genotypes was significantly associated with visceral obesity, carotid intima-medial thickening and insulin sensitivity. CONCLUSION: ACE genotypes was not significantly associated with visceral obesity, carotid intima- medial thickening and insulin sensitivity. However, to explore the true associations of ACE gene polymorphism with insulin resistance and ather-osclerosis, we further suggest and recommend prospective studies.
- Insulin Secretion, Insulin Sensitivity and Body Fat Distribution Patterns in Patients with Impaired Glucose Tolerance.
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Jin Hwa Lee, Yeon Ah Sung, Nan Ho Kyung, Yeon Jin Jang
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Korean Diabetes J. 1999;23(5):647-660. Published online January 1, 2001
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- BACKGROUND
Type 2 diabetes mellitus(DM) is characterized by impaired insulin secretion and decreased insulin sensitivity, and often preceded by impaired glucose tolerance (IGT). To determine the relative importance of impaired insulin secretion and insulin resistance in development of type 2 DM, we evaluated body fat distribution patterns, insulin secretion and sensitivity in patients with IGT. METHODS: Thirty-six patients with IGT and age and weight matched twenty-four control subjects, were recruited from urban diabetes incidence cohort. Fasting serum glucose and insulin were measured. Body fat distribution pattern was assessed by waist to hip ratio (WHR), percent body fat and fat mass measured by bioelectrical impedence analyzer, and visceral to subcutaneous fat ratio (VSR) at the level of umbilicus using the computed tomography. Using insulin modified intravenous glucose tolerance test, insulin sensitivity was measured as minimal model derived sensitivity index (S(I)), and insulin secretion was measured as acute insulin response to glucose (AIR(g)) and beta-cell disposition index (AlR(g) X Sr). RESULT: l) In the patients with IGT, AIR(g)X S(I)(p<0.01) and area under the curve of insulin (AUC(I))(p<0.01) were significantly decreased compared with control subjects and age was greater than control subjects without statistical significance (p=0.17). 2) In the patients with IGT, body fat distribution patterns, indices of insulin secretion and sensitivity were not different according to the presence of family history of DM. AIR, and S(I) were negatively correlated in control subjects (r=-0.38, p=0.08) and the patients with IGT without family history of DM (r=-0.37, p=0.10), but not in the patients with IGT with family history of DM. 3) In the patients with IGT, indices of insulin secretion and sensitivity were not different according to body mass index (BMI). In both obese (BMI>=25 kg/m ) and non-obese (BMI<25 kg/m) patients with IGT, AIR(g)(p<0.05) and AIR(g) X S(I) were significantly decreased compared with control subjects (p<0.01). 4) In control subjects, age (p<0.05) and body fat mass (p<0.05) were significantly associated with AIR(g) X S(I) by multiple regression analysis. In the patients with IGT, body fat mass was significantly associated with AIR(g)(p<0.01) and AUC(I)(p<0.01), and BMI(p<0.01) was significantly associated with S(I). CONCLUSION: In patients with IGT, impaired insulin secretion was more prominent than decreased insulin sensitivity as compared with control subjects regardless of obesity and the presence of family history.
- Prevalence and Risk Factors of Erectile Dysfunction in Diabetic Men by Self-Reported Questionnaires.
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Jin Hwa Lee, Jee Young Oh, Young Sun Hong, Yeon Ah Sung, Nan Ho Kyung, Woo Sik Chung, Eun Young Choi
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Korean Diabetes J. 1998;22(4):538-545. Published online January 1, 2001
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Erectile dysfunction is the consistent inability to achieve or sustain an erection of suffieient rigidity for sexual intercourse. Erectile dysfunction is an important cause of decreased quality of life in diabetic men. The prevalence of ereciile dysfunction has been reported to be three times higher in diabetic men than nondiabetics. Erectile dysfunction in diabetic men has been associated with increased age, poor glycemic control, smoling, alcohol intake, depression, and microvascular diabetic complication. Our purpose was to determine the prevalence of erectile dysfunction in diabetic men and to assess risk factors re]ated to erectile dysfunction in diabetes mellitus. METHODS: From l53 diabetic men visiting Ewha Womans University Hospital from March, 1997 to March, 1998, we analyzed the self-reported questionnaires. Three questions about erection and one question about overall sexual satisfaetion were given and the answer to each question was categorized into 5 degrees according to the severity of sexua] dysfunction. Erectile dysfunction was diagnosed when any answer for erection showed a degree lower than 4. We obtained the history of smoking, alcohol and hypertension, and measured the current weight and height. Fasting glucose, HBA 1c and lipid profile were me measured. We also evaluated for the presence of diabetic retinopathy, nephropathy and neuropathy. RESULTS: 1) The self-reported prevalence of erectile dysfunction in diabetic men was 75.5 % in this study. 2) In the patients with erectile dysfunction, age, duration of diabetes mellitus, HbAlc, and systolic blood pressure were significantly higher, and BMI and triglyceride significantly lower than in the patients without erectile dysfunction. 3) The prevalence of erectile dysfunction was increased with aging and increasing duration of diabetes mellitus, HBA. was significantly positively related and BMI was inversely related to erectile dysfunction. 4) Age and HbA 1c were independently and positively related to erectile dysfunction by multiple logistic regression. 5) The erectile dysfunction was significantly associated with diabetic autonomic neuropathy and retinopathy. CONCLUSION: The prevalence of self-reported erectile dysfunction in diabetic men was 75.5 % in this study, and it was significantly related to aging and the degree of the glycemic control.
- Dehydroepiandrosterone-Sulfate, Sex Hormone Binding Globulin, Body Fat Distribution Pattern and Insulin Resistance in Women.
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Young Sun Hong, Jee Young Oh, Yeon Ah Sung, Nan Ho Kyung, Yeon Jin Jang
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Korean Diabetes J. 1998;22(3):328-337. Published online January 1, 2001
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Sex hormone-binding globulin (SHBG) has been known to be associated with obesity, central fat accumulation and insulin resistance and thought to be a indirect marker for androgenicity in women. The relationships between circulating dehydroepiandrosterone(DHEA). dehydroepiandrosterone sulfate(DHEA-S) levels and body fat accumulation are still controversial. We conducted a cross-sectional study to eva]uate the relationships between serum levels of SHBG, DHEA-S, body fat distribution pattern and insulin sensitivity in women. METHODS: We tested 57 women(age 30~65yr; BMI 18.5~32.8kg/m, 45 premenopausal on the 5~10 day of the menstrual cycle, 12 postmenopausal who were not using hormone replacement therapy) with varying degree of glucose tolerance(32 normal glucose tolerance(NGT), 17 impaired glucose tolerance(IGT) and 8 newly diagnosed diabetes). lnsulin sensitivity was measured as minimal model derived sensitivity index(S) using insulin modified IV glucose tolerance test and fasting serum levels of SHBG and DHEA-S were measured by RIA. Body fat distribution pattern was assessed by waist to hip ratio(WHR),% body fat measured by bioelectrical impedance analyzer, subcutaneous fat area(SFA), visceral fat area(VFA) and VFA to SFA ratio(VSR) at the level of umbilicus using the computed tomography. RESULTS: 1) Measured SHBG and DHEA-S levels were not significantly different among subjects with NGT, IGT and diabetes. 2) SHBG was inversely associated with age, BMI, WHR, diastolic blood pressure, VFA, SFA, VSR,% body fat, fasting insulin and positively associated with S, whereas DHEA-S did not show any significant correlation with above variables except diastolic blood pressure. 3) SHBG level was significantly lower(p<0.05) and DHEA-S level was insignificantly lower (p=0.05) in postmenopausal women than in premenopausal women but the significance disappeared after adjustment for age, BMI, WHR and% body fat. 4) BMI was independently and negatively related to S, WHR and fasting insulin to SHBG by multiple regression analysis. CONCLUSION: We confirmed that SHBG was independently associated with central obesity and fasting hyperinsulinemia. However, S was independently associated with BMI only. It suggested that hyperinsulinemia in insulin resistance might cause the decreased level of SHBG even thaugh the directionality of the association was uncertain because of a cross-sectional nature of this study.
- 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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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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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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