- Inducible Nitric Oxide Synthase (iNOS) Expression in the Hypoxic Injury to Pancreatic Beta (MIN6) Cells.
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Seung Hyun Ko, Seung Bum Kim, Kyung Ryul Ryu, Ji Won Kim, Yu Bai Ahn, Sung Dae Moon, Sung Rae Kim, Jung Min Lee, Hyuk Snag Kwon, Kun Ho Yoon, Ki Ho Song
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Korean Diabetes J. 2006;30(5):336-346. Published online September 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.5.336
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- BACKGROUND
Islet transplantation is an alternative potential strategy to cure type 1 diabetes mellitus. However, two or more donors are usually needed for one recipient because a substantial part of the graft becomes nonfunctional due to several factors including hypoxia. Though hypoxic exposure of pancreatic beta cells has been reported to induce apoptotic cell death, the molecular processes involved in hypoxia-induced cell death are poorly understood. In type I diabetes, Nitric Oxide (NO) is known as an important cytokine, involved in the pathogenesis of beta cell dysfunction. Pancreatic beta cells are sensitive to the induction of inducible nitric oxide synthase (iNOS) when stimulated by TNF-a or IL-1beta. But contribution of iNOS in response to hypoxia is not yet fully understood. METHODS: Mouse insulinoma cells (MIN6) were incubated in an anaerobic chamber (75% N2/15% CO2/5% H2) for up to 12 hours. Cell viability was measured after AO/PI staining. Caspase-3 activation was also determined using Western blot analysis. Nitric Oxide (NO) release into culture medium was measured using a Griess reagent. The expression of iNOS and PDX-1 mRNA and iNOS protein was examined using real time PCR and Western blot analysis. RESULTS: Marked cell death was observed within 6 hours after hypoxic exposure of MIN6 cells (control, < 5%; 2 hr, 11.0+/-7.6%; 6 hr, 46.2+/-12.8%, P < 0.05). Immunoreactivity to activated caspase-3 was observed at 2, 4 and 6 hrs. NO production was increased in a time dependent manner. Expression of iNOS mRNA and protein was significantly increased at 4 and 6 hour after hypoxia. iNOS expression was confirmed by immunostaining. Of note, Pdx-1 mRNA expression was markedly attenuated by hypoxic treatment. Pretreatment with a selective iNOS inhibitor, 1400 W, significantly prevented beta cell death induced by hypoxic injury. CONCLUSION: Our data suggest that iNOS-NO play an important role in hypoxic injury to MIN6 cells. Therefore, iNOS-NO might be a potential therapeutic target for improving engraftment of the transplanted islets and suppression of iNOS would be helpful for prevention of beta cells damage to hypoxic injury.
- Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.
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Seung Hyun Ko, Hyuk Sang Kwon, Jung Min Lee, Sung Rae Kim, Jae Hyung Cho, Ki Dong Yoo, Yong Moon Park, Won Chul Lee, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bai Ahn
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Korean Diabetes J. 2006;30(3):226-235. Published online May 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.3.226
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- BACKGROUND
Diabetic autonomic neuropathy has a significant negative impact on survival and quality of life in type 2 diabetic patients. Especially cardiovascular autonomic neuropathy (CAN) is clinically important, because of its correlation to cardiovascular death. Therefore, we investigated the prevalence of CAN in Korean type 2 diabetic patients. METHODS: 1798 type 2 diabetic patients, 727 males and 1071 females, visited Diabetes Clinic at St. Vincent Hospital, Korea, were included from January 2001 to December 2005. Clinical evaluation, laboratory test and assessment of diabetic complication were completed. Standard test for CAN were performed: 1) heart rate variability (HRV) during deep breathing (E/I ratio) 2) Valsalva maneuver 3) 30:15 ratio 4) blood pressure response to standing. CAN score was determined according to the results of the test as following: 0 = normal, 1 = abnormal. RESULTS: Mean age and diabetic duration of patients were 56.7 +/- 10.9, and 9.4 +/- 7.5 years. Normal and abnormal CAN were detected in 815 (45.3%) and 983 (54.7%) of the patients, respectively. Abnormal E/I, valsalva, and 30:15 ratio were found in 333 (18.5%), 717 (39.9%), and 546 (30.4%) patients, respectively. Age, diabetic duration, postprandial hyperglycemia, HbA1c, C-reactive protein, and microalbumuria levels were significantly different between normal and abnormal CAN groups. 49 (6.0%) patients of normal and 100 (10.2%) patients of abnormal CAN group showed previous attack of stroke (P = 0.004). In addition, diabetic foot was more frequent in patients with CAN (normal vs. abnormal, 14 (1.7%) vs. 73 (7.4%), P < 0.05). CONCLUSION: CAN is frequently found in Korean type 2 diabetic patients. It was associated with diabetic duration, uncontrolled diabetes, increased albumin excretion rate, presence of retinopathy, postprandial hyperglycemia.
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- Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea
Sol Jae Lee, Su Jin Jeong, Yu Chang Lee, Yong Hoon Lee, Jung Eun Lee, Chong Hwa Kim, Kyung Wan Min, Bong Yun Cha Diabetes & Metabolism Journal.2017; 41(4): 275. CrossRef - Screening of Autonomic Neuropathy in Patients with Type 2 Diabetes
Bo Kyung Koo Diabetes & Metabolism Journal.2014; 38(5): 346. CrossRef - Decision trees and multi-level ensemble classifiers for neurological diagnostics
Herbert F. Jelinek, Jemal H. Abawajy, Andrei V. Kelarev, Morshed U. Chowdhury, Andrew Stranieri AIMS Medical Science.2014; 1(1): 1. CrossRef - Correlation between Predictors for Diabetic Gastroparesis and Gastric Emptying Scintigraphy
Kyung-Ju Lee, Kyoung-Ho Ryu, Jin-Ook Chung, Dong-Hyeok Cho, Dong-Jin Chung, Min-Young Chung Chonnam Medical Journal.2009; 45(3): 175. CrossRef - Epidemiologic Characteristics of Diabetes Mellitus in Korea: Current Status of Diabetic Patients Using Korean Health Insurance Database
Ie Byung Park, Sei Hyun Baik Korean Diabetes Journal.2009; 33(5): 357. CrossRef - The Status of Diabetes Mellitus and Effects of Related Factors on Heart Rate Variability in a Community
Kyeong-Soon Chang, Kwan Lee, Hyun-Sul Lim Korean Diabetes Journal.2009; 33(6): 537. CrossRef
- Clustering Characteristics of Risk Variables of Metabolic Syndrome in Korean Rural Populations.
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Yong Moon Park, Hyuk Sang Kwon, Sun Young Lim, Jin Hee Lee, Sung Rae Kim, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yong Gyu Park, Dong Suk Kim, Kwang ho Meng, Won Chul Lee
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Korean Diabetes J. 2006;30(3):177-189. Published online May 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.3.177
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Abstract
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- BACKGROUND
The risks of both type 2 diabetes mellitus and cardiovascular disease are mainly associated with the metabolic syndrome which is characterized by clustering of metabolic risk factors, including abdominal obesity, glucose intolerance, hypertension, and dyslipidemia. This study aimed to examine the relations among metabolic risk variables and the underlying structure of the metabolic syndrome that unites related components. METHODS: Subjects were selected by stratified random cluster sampling among persons aged over 40 years from a rural area. Waist circumference, BMI, fasting glucose, fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and diastolic blood pressure were used as risk variables of metabolic syndrome. Factor analysis, a multivariate correlation statistical technique, was performed on a dataset from nondiabetic 3,443 men and women without history of coronary heart disease. RESULTS: Exploratory factor analysis identified three factors in both gender (obesity, hypertension, and dyslipidemia-insulin resistance in men; obesity-insulin resistance, hypertension, and dyslipidemia in women). Fasting insulin was a common contributor to the structure of metabolic syndrome in male subjects, smokers and alcohol drinking group. Confirmatory factor analysis based on the results of exploratory factor analysis revealed that metabolic syndrome was represented primarily by obesity factor in men, obesity-insulin resistance factor in women, and that dyslipidemia factor was highly correlated with obesity factor in men, with insulin resistance factor in women. CONCLUSION: Underlying structure of metabolic syndrome was different between men and women, and obesity might be a primary target for prevention of both type 2 diabetes mellitus and cardiovascular disease in Korea.
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Citations
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- Disjoint factor analysis with cross-loadings
Maurizio Vichi Advances in Data Analysis and Classification.2017; 11(3): 563. CrossRef - Factors associated with control of blood pressure among elderly people diagnosed with hypertension in a rural area of South Korea: The Chungju Metabolic Disease Cohort Study (CMC study)
Hong-Seok Lee, Yong-Moon Park, Hyuk-Sang Kwon, Jin Hee Lee, Kun-Ho Yoon, Ho Young Son, Dong Suk Kim, Hyeon Woo Yim, Won-Chul Lee Blood Pressure.2010; 19(1): 31. CrossRef - Optimal Waist Circumference Cutoff Value Reflecting Insulin Resistance as a Diagnostic Criterion of Metabolic Syndrome in a Nondiabetic Korean Population Aged 40 Years and Over: The Chungju Metabolic Disease Cohort (CMC) Study
Yong-Moon Park, Hyuk-Sang Kwon, Sun Young Lim, Jin-Hee Lee, Kun-Ho Yoon, Ho-Young Son, Hyeon Woo Yim, Won-Chul Lee Yonsei Medical Journal.2010; 51(4): 511. CrossRef - Prevalence, Awareness, Treatment, and Control of Hypertension Among People Over 40 Years Old in a Rural Area of South Korea: The Chungju Metabolic Disease Cohort (CMC) Study
Hong-Seok Lee, Yong-Moon Park, Hyuk-Sang Kwon, Jin-Hee Lee, Young Joon Park, Sun Young Lim, Seung-Hwan Lee, Kun-Ho Yoon, Ho-Young Son, Dong Suk Kim, Hyeon Woo Yim, Won-Chul Lee Clinical and Experimental Hypertension.2010; 32(3): 166. CrossRef
- Development of Adult Porcine Islet Isolation Method for Xenotransplantation.
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Sung Rae Kim, Kun Ho Yoon, Hyuk Sang Kwon, Sun Hee Suh, Seung Hyun Ko, Jung Min Lee, Soon Jib Yoo, Yoo Bae Ahn, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
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Korean Diabetes J. 2004;28(2):75-87. Published online April 1, 2004
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AND PURPOSE: Xenotransplantation using porcine islet cells might be an alternative to allotransplantation, which has been limited due to the lack of donors. Various researches using porcine islet cells have been performed in foreign countries; however, they have never been studies in Korea. Therefore, the purpose of this study was to explore the possibility of thise new treatment for cases of diabetes by establishing of improved islet isolation skill. METHODS: The pancreas and islets were extracted from pigs weighing around 100kg. To establish an islet isolation method, the islet yield, purity and the distribution size of the isolated islets were step wise compared in various ways, and then the superior method adopted. To determine the conveyance method after organ extraction, the conveyance method of pouring collagenase P was compared with the conveyance method of injecting Custidol. For digestion, the mechanical shaking and static incubation methods were also compared. To isolate islets from the digested pancreata, isolation methods were analyzed using 3 and 4 layers' Ficoll. The islet yield was appraised after their isolation using the optimized islet isolation method. To assess the results of the islet isolation, appraised the purity and the survival rates of cells, the insulin secretion resulting from the glucose stimulation test was examined. RESULTS: The method of injecting 4degrees C Custidol was effective for the conveyance and storage of the isolated pancreas in comparison with an injection of collagenase P(3465+/-1488 IEQ/g pancreas vs. 48+/-1.7 IEQ/g pancreas, p<0.01). The digestion method was superior to the mechanical shaking method at keeping a stable condition(3465+/-1488 IEQ/g pancreas vs. 1265+/-141.4 IEQ/g pancreas, p<0.01). Ficoll isolation using 3 layers gave the same results as using 4 layers. The average weights of the isolate Pancreatic islets was 23.8+/-3.3g. The numbers of islets per gram was 3465+/-1488.2(IEQ), with a the purity of 86.3+/-2.0%, and a survival rate of over 95%. The insulin secretion caused by glucose stimulation substantially increased in concentration from 24 to 72 hours(24hr: 5mM 3.12mU/mL --< 20mM 6.79mU/mL(2.17 fold), 72hr: 5mM 2.38mU/mL --< 9.93mU/mL(4.17fold))
- The Effect of Nitric Oxide on Insulin Binding and Insulin Receptor Recycling in Bovine Aortic Endothelial Cells.
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Hyuk Sang Kwon, Oak Kee Hong, Hee Soo Kim, Jung Min Lee, Sung Rae Kim, Sung Dae Moon, Sang Ah Jang, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
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Korean Diabetes J. 2003;27(3):213-227. Published online June 1, 2003
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The coexistence of insulin resistance and endothelial dysfunction is commonly observed in a variety of metabolic and cardiovascular disorders, including athero-sclerosis and type 2 diabetes mellitus. Because nitric oxide (NO), or nitric oxide synthase (NOS), has been suggested as a significant contributing factor in the development of endothelial dysfunction and insulin resistance, reactive NO or NOS were investigated to see if they contribute to the insulin internalization pathway. METHODS: The production of NO (Nitrite), the expression of eNOS (endothelial NOS), insulin binding and the insulin receptor internalization and recycling, following 48 hours of incubation with bradykinin (BK), acetylcholine (Ach), NG-monomethyl- L-arginine (L-NMMA) and N-nitro-L-arginine methylester (L-NAME) in Bovine aortic endothelial cells (BAECs), were examined. RESULTS: The results were as follows: 1. In relation to the time course, the production of eNOS was increased, but was decreased after 8 hours of incubation. The production of eNOS in the L-NMMA and L-NAME treated groups was significantly decreased compared with that of the controls (p<0.05). 2. The specific insulin bindings to the receptors of the endothelial cells were maximized within 20 mins, and then decreased. At 20 mins, the binding rate of the L-NMMA treated group was significantly decreased compared to that of the controls. At a concentration of 0.4ng/ml of unlabelled insulin, the specific insulin binding of the L-NMMA treated group was significantly decreased compared to that of the controls (p<0.05). 3. The internalization of 125I-insulin into the endothelial cells, as assessed by the acid washing dissociation method, occurred rapidly. The internalized radioactivity of 125I-insulin, at 20 mins, was significantly increased in the BK and Ach groups compared with the controls (p<0.05). 4. The recycling of the internalized insulin receptors showed no significant differences between the study groups, but the recycling was slightly delayed compared with controls in the Ach group. CONCLUSION: In conclusion, the NO generating substances, BK and Ach, and the inhibitory substance, L-NMMA, may influence the binding and internalization of insulin-insulin receptors. Our results suggest that NO might contribute to the transcytosis of insulin in BAECs
- Selective beta-Cell Loss and alpha-Cell Expansion in Islets of Type 2 Diabetic Patients.
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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
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Korean Diabetes J. 2001;25(2):164-177. Published online April 1, 2001
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Abstract
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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.
- Effects of Cilostazol on Insulin Resistance in OLETF Rats.
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Sung Rae Kim, Ki Hyun Baek, Seung Hyun Ko, Jung Min Lee, Sang Ah Chang, Yoo Bae Ahn, Soon Jib Yoo, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
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Korean Diabetes J. 2001;25(1):63-70. Published online February 1, 2001
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Insulin resistance is one of the major pathophysiology of type 2 diabetes mellitus. It is reported that cilostazol and cyclic AMP phosphodiesterase inhibitor has the anti-platelet effect as well as an improvement of hypertriglyceridemia in addition to vasodilatation. Furthermore, the previous reports indicated that there is a positive relationship between insulin resistance and dyslipidemia. Thus, we investigated the effects of cilostazol on insulin resistance in OLETF rats using the euglycemic hyperinsulinemic glucose clamp technique, and lipid levels. METHODS: Fifteen five months old OLETF rats were fed for 4 weeks(8 treated with cilostazol and 7 were control), and compare to 20 same aged LETO rats (8 treated with cilostazol and 12 were control) through the glucose infusion rate on euglycemic hyperinsulinemic glucose clamp and lipid profiles. RESULTS: The glucose infusion rate was higher in the cilostazol treated OLETF rats than in the non-cilostazol treated OLETF rats (0.021+/-0.0031 vs 0.027+/-0.0036 mL/min). The levels of free fatty acids (2424.8+/-652.7 vs 1061.8+/-223.2 Eq/L), total cholesterol (145.7+/-17.9 vs 115.4+/-7.6 mg/dL) and triglyceride (146.5+/-46.6 vs 76.1+/-12.5 mg/dL) of cilostazol treated OLETF rats were significantly lower than those of non-cilostazol treated OLETF rats. CONCLUSION: This study result suggest that cilostazol may improve the insulin resistance through the improvement of dyslipidemia in OLETF rats.
- Changes in the Amount and Function of Gi Protein in the Liver Cells of Streptozotocin-Induced Diabetic Rats.
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Sun Myeong Ock, Hyun Shik Son, Oak Kee Hong, Jung Min Lee, Sung Rae Kim, Sang Ah Chang, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
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Korean Diabetes J. 2000;24(6):666-677. Published online January 1, 2001
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The functional and expressional changes of Gi proteins in diabetes have been investigated extensively, no agreement has been reached in the results. Moreover, studies using rats with different diabetic duration, and using subunits (Gialpha) of Gi proteins are lacking in literatures. Thus, we assessed the changes according to the duration of diabetes and examined the expressional changes of Gialphaand functional changes of Gi proteins in hepatocytes from streptozotocin-induced diabetic rats. METHODS: Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes ; 1, 2, 3 and 5 weeks after the onset of diabetes, livers from the control and diabetic rats were fractionated into homogenate, interface, and plasma membrane. The levels of Gialpha1&2, Gialpha3 were quantified with western blots in each fraction. The functional changes of Gi proteins were evaluated by performing pertussis toxin-catalyzed ADP-ribosylation and measuring GTP S binding activity. RESULTS: 1) Gialpha2 and Gialpha3 were present mainly in the plasma membrane of hepatocytes in the diabetic and control rats, but the levels of these subunits were significantly higher in the diabetic rates than in the control rats (p<0.01). The levels of these subunits were not affected by the duration of diabetes. 2) In streptozotocin-induced diabetic rats, the levels of ADP-ribosylation of Gi proteins in liver plasma membranes decreased when pertussis toxin-catalyzed ADP-ribosylation was performed with liver tissues. However, the levels of these proteins were not affected by the duration of diabetes. 3) For the GTP S binding activity of Gi proteins in liver plasma membranes, the diabetic rats showed significantly less activity than the control rats (p<0.01). However, the activity was not affected by the duration of diabetes. The activity was somewhat restored by the insulin treatment of liver plasma membranes in diabetic rats. CONCLUSION: These results suggest that the insulin-deficient diabetic state induces the quantitative and functional changes in Gi proteins of hepatocytes regardless of the duration of diabetes. Therefore, these changes in Gi proteins may be the important compensatory reactions for the insulin resistance occurring in the insulin deficient state.
- The Effect of Increased Beta Cell Mass on Glucose Tolerance in Rat.
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Eun Sook Oh, Kun Ho Yoon, Sun Hee Seo, Sook Young Lee, Seung Hyun Ko, Won Young Lee, Sung Rae Kim, Moo Il Kang, Bong Yon Cha, Kwang Woo Lee, Ho Young Son, Sung Goo Kang
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Korean Diabetes J. 2000;24(6):629-640. Published online January 1, 2001
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- BACKGROUND
The aim of the present study is to evaluate the effect of increased beta cell mass by continuous 96-hour 50% glucose infusion on glucose tolerance in insulin resistance state induced by high fat diet in normal Sprague-Dawley rats. METHODS: The adult Sprague-Dawley rats weighing 200-250 gm were infused with 50% glucose or 0.45% saline via external jugular vein catheter for 96 hours. The both groups of rats were then randomly stratified into the two subgroups, and fed either high fat diet (54% of energy from fat) or normal rat chow (8.6% of energy from fat) for 4 weeks. On day 28, blood was collected for measuring the serum concentration of insulin, and oral glucose tolerance test (2 gm/kg body weight) was performed after overnight fasting. The beta cell mass was counted with the morphometric point-counting technique of Weibel. RESULTS: After the 96 hour infusion, the percentage of beta cell mass was significantly increased in glucose-infused rats when compared to the saline-infused group (p=0.03) and maintained up to day 28. Body weight gains were significantly greater in glucose infused rats than those of saline infused group (Increased value of weight : 142.9+/-15.2 g in glucose infused rats vs 125.3+/-21.1 g in saline infused rats, p=0.01). In the saline infusion-high fat diet group, the number of rats with impaired glucose tolerance was higher than those of other group (p<0.005). The glucose values at 90 minute and 120 minute were higher in saline infusion-high fat diet group than in glucose infusion-high fat diet group (p< 0.05). CONCLUSION: Our findings suggest that the increased beta cell mass has a favorable effect on glucose tolerance in insulin resistance state which were evoked by high fat diet.
- Quantification of the Pancreatic -cell Mass in Normal and Type 2 Diabetic Subjects in Korea.
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Kun Ho Yoon, Seung Hyun Ko, Jung Min Lee, Sung Rae Kim, Sun Hee Seo, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Yong Gui Kim, In Sung Moon, Myung Deuk Lee, Dong Ku Kim, Kyo Young Lee, Chan Suk Kang, Byung Ki Kim
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Korean Diabetes J. 2000;24(5):524-532. Published online January 1, 2001
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There have been several reports about insulin secretory impairment in non-obese type 2 diabetic patients and even in impaired glucose tolerant subjects in Korea. Insulin secretory impairment might be induced by insufficient beta-cell mass, functional defects of beta-cells or both. To clarify the cause of impaired insulin secretion in type 2 non-obese diabetic patients in Korea, beta- cell masses were quantified in normal and type 2 diabetic subjects. METHOD: Normal pancreases were procured by 6 heart-beating non-diabetic donors under informed consent from relatives and approval of the university ethical committee. To quantify the beta cell mass and insulin content in various part of the pancreas, first we divided it into 3 parts: head, body and tail, and then each three parts were weighed and subdivided again into 8 segments equally. For diabetic patients, tissue sections were obtained from 15 partial or total pancreatectomized type 2 diabetic patients of any causes. After being fixed, tissues were immunostained using the Streptavidin-biotin-peroxidase method with anti-insulin antibody. Beta cells were counted by point count method. RESULTS: The mean value of total pancreas weight of normal subjects (n=6) was 77.1+/-14.6 g, that of mean relative volume of beta cells in the pancreas was 2.1+/- 0.9%, ranging from 1.4% to 3.1% (head 2.3+/-0.6%, body 1.8+/-0.2%, tail 2.2+/-0.4%). Mean value of total beta cell mass which was calculated from relative volume of beta-cells and weight of each portions was 1.3+/-0.3 g, ranging from 1.2 g to 1.9 g (head 0.6+/-0.3 g, body 0.4+/-0.2 g, tail 0.4+/-0.2 g). Mean insulin content per pancreas was 63.6+/-46.6 g, ranging from 27.8 to 137.2 g/pancreas (head 25.1+/- 19.1 g, body 20.8+/-15.5 g, tail 17.7+/-14.9 g). In diabetic patients, relative volume of beta cells in tissues were variable from 0.4% to 2.8% and there was good correlation between beta-cell mass and body mass index of the diabetic patients. However we can't find the correlation among relative volume of beta-cell, (r2=0.55, p<0.05) duration of diabetes and age. Remarkable heterogeneity for loss of beta-cells in the islets of diabetic patients was observed even in the same lobe of pancreas. There were no evidence of lymphocytic infiltration in the islets. CONCLUSION: Insufficient beta cell mass seems to be a main cause for insulin secretory impairment in non-obese type 2 diabetic patients in Korea.
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