- The Study of Alteration of Beta Cells in Pancreatic Islets, Glusoce Metabolism and Insulin Secretion in Low Dose Streptozotocin Indeced Type 2 Diabetic Rat Model.
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Young Goo Shin, Hong Seung Kim, Mi Deok Lee, Young Uck Kim, Ho Suck Kang, Tae Sun Hwang, Choon Hee Chung
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Korean Diabetes J. 1999;23(3):256-268. Published online January 1, 2001
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- BACKGROUND
Korean diabetes is different from western diabetes due to the racial differences in genetic factors and susceptability. It has recently been suggested that thrifty phenotype hypothesis is related to the recent increase in prevalence of Korean diabetes, but we have little evidence about that. We obtained basic materials in the animal model of type 2 diabetes mellitus and conducted a morphologic study of the beta cell change, insulin secreting capacity, and glucose metabolism. METHODS: To obtain the reference data of a non-insulin dependent diabetic animal model, we performed the intraperitoneal glucose tolerance test (IPGTT), hyperinsulinemic euglycemic clamp and immunobistochemical staining on the sacrificed pancreatic tissues on a Sprague-Dawley male rat into which streptozotocin (STZ) had been injected during the early neonatal period. The study groups consisted of a normal control group with citrate buffer injection, a group with injection of 50 ug STZ per kg of weight and a group with injection of 75 ug STZ per kg of weight. STZ was injected within 12 hours after birth. RESULTS: l. Although, STZ injected groups had lower body weight than the control group 7 weeks after birth, there were no differences during 14 weeks. 2. The IPGTT results showed that the average level of whole blood glucose concentration of the group with 50 ug STZ per kg of weight was higher than that of the control group at 7 and 14 weeks after birth. The mean serum insulin concentration of the 75 ug STZ per kg of weight injected group was lower than that of the control group at 7 weeks after birth, but it was higher than that of the control group at 14 weeks. 3. The hyperinsulinemic euglycemic clamp study showed that the average level of peripheral glucose disposal rate of the STZ injected groups was lower than the control group, but there were no differences in the study groups. 4. Pancreatic islet showed decreased beta cell mass and increased beta cell size in the STZ injected groups but the BrdU labelling index was not different between the control and study groups. CONCLUSION: STZ injection into neonatal Sprague-Dawley male rats may result in a diabetic status due to both decreased insulin secretion and increased insulin resistance, which gives us useful reference data for type 2 diabetes mellitus in the animal model.
- Plasma Proinsulin Levels among the Control, Impaired Glucose Tolerance and Type 2 Diabetes Mellitus during Oral Glucose Tolerance Test.
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Mi Deok Lee, Young Uck Kim, Hong Seung Kim, Young Goo Shin, Choon Hee Chung
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Korean Diabetes J. 1999;23(2):147-154. Published online January 1, 2001
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Increased secretion of proinsulin has been associated with beta-cell dysfunction. Hyper-proinsulinemia is suggested to be a predictor for the progression of IGT to type 2 DM. In this study, we compared the concentration of insulin, C-peptide and proinsulin levels among the control group, IGT and type 2 DM group during the oral glucose tolerance test. We investigated whether hyperproinsulinemia was an effective predictor of beta-cell impairment befre the clinical onset of type 2 diabetic subjects. METHODS: We studied proinsulin, insulin(using an assay that display appreciable cross-reactivity with proinsulin) and proinsulin:insulin ratio during the oral glucose tolerance test in 14 controls, 20 IGT and 20 type 2 DM. We also compared proinsulin, proinsulin response areas and proinsulin:insulin ratio among the three groups. RESULTS: There were no significant differences in the baseline and 30min proinsulin levels among three groups. However, proinsulin response areas in IGT were higher than those in other groups. Baseline proinsulin/insulin ratio and post-load proinsulin/ insulin ratio were not significantly different among the three groups. In IGT group, the proinsulin response after glucose loading was rapidly increased, but was blunted in diabetic patients. CONCLUSION: We suggest that pancreatic beta cell dysfunction was ongoing before the clinical onset of DM and hyperproinsulinemia, especially the proinsulin response areas during oral GTT may be a predictor for the development of type 2 DM.
- Estimation of Cut-off Point of Fasting Blood Glucose Predicting Pancreaticbeta-cell Decompensation During Oral Glucose Tolerance Test.
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Mi Deok Lee, Hong Seung Kim, Young Uk Kim, Young Goo Shin, Chang Ho Song, Young Jun Won, Choon Hee Chung
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Korean Diabetes J. 1998;22(4):513-521. Published online January 1, 2001
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The secretory dysfunction of pancreatic B-cell is one of the important in the pathogenesis of NIDDM. And the conversion from IGT to DM is developed by the exhaustion and decompensation of 0-cell. So our purp was estimating the cut-off point of fasting blood sugar predicting B-cell decompensation during OGTT. METHOD: The clinical characteristics and anthropometric parameters were determined in all subjects. 75 g ora] glucose tolerance tests were performed with serial blood sampling to measure plasma glucose levels, insulin and C-peptide levels. And we calcolated insulin response areas and C-peptide response areas. RESULTS: l) The basal C-peptide levels were elevated in IG1' and DM group. however, post-load 30min C-peptide and 30min insulin levels were significantly decreased in DM group compared with normal and IGl. 2) IGT group showed the highest C-peptide response areas among three groups. 3) The relationships between fasting plasma glucose, C-peptide & insulin levels showed that basal C-peptide level had turning point at 6.7 mmol/L of fastiing glucose, basal insulin level at 6.5 mmol/L, 30 min C-peptide at 6.2 mmol/1, 30 min insulin at 5.8 mmol/L and C-peptide response area at 7.0 mmol/L. Conclusion : Above result suggest that the fasting plasma glucose of 7.0 mmol/L may be the cut-off point of pancreatic B-cell decompensation.
- Measurement of Anti-GAD antibody by EIA and RIA Methods in Korean Diabetic patients: Study for pathogenesis of slowly progressive IDDM.
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Han Hyo Lee, Young Goo Shin, Hee Sun Kim, Chang Young Kim, Yon Soo Jeong, Hong Seung Kim, Deok Woo Park, Kap Jun Yoon, Choon Hee Chung
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Korean Diabetes J. 1997;21(3):231-242. Published online January 1, 2001
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Sometimes it is difficult to discriminate between IDDM and NIDDM among adults with DM. Some NIDDM patients have autaantibodies and follow the course of IDDM, We call them as slowly progressive IDDM(SPII)DM). Since anti-GAD (Glutamic acid decarboxylase') Ab can be detected both before and for a long pe.riod after the diagnosis of DM it is helpful for the diagnosis of autoimmune diabetes. METHODS: The subjects were 68 diabetic patients who were admitted at Wonju Christian Hospital from May 1994 to Feb 1996. We classified them as IDDM, NIDDM and SPIDDM. We analyzed the following: a studied basic clinical study, oral glucose tolerance test, HLA DR typing, IgM anti-viral Abs, ICA, IAA and nti-GAD Ab. RESULTS: In measurement of anti-GAD Ab, IRMA was more sensitive than EIA. Anti-GAD Ab prevalence was significantly higher in IDDM patients than in NIDDM patients. By IRMA method, Anti-GAD titers showed significant correlation among VELISA, HEXT, IRMA and RSR methods(p<0.001). CONCLUSION: As seen by the results above, the positivity of antiGAD Ab by EIA and RIA method was lower for Korean diabetic patients than for Caucasians. We suggest that the other mechanisms as well as autoimmunity may be involved in the pathogenesis of SPIDDM in Koreans. We need follow-up studies about the clinical and immunogenetic characteristics of these patients.
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