- 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.
- Effect of Pancreatic Islet Autotransplantation after Pacreatectomy in Patients with Benign Pancreatic Tumor.
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Jae Hwan Jee, Byung Wan Lee, Seung Hoon Oh, Ji Youn Kim, Hyun Jin Kim, Jung Hyun Noh, Sung Ho Choi, Jae Hoon Chung, Yong Ki Min, Myung Sik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2004;28(2):88-100. Published online April 1, 2004
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Abstract
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- BACKGROUND
Previously, in patients suffering from insulin deficient DM after a partial or total pancreatectomy as treatment for a benign pancreatic tumor, insulin treatment has only led to severe fluctuation in the blood glucose level, and frequently to sudden hypoglycemia due to glucagon deficiency and lack of delicate insulin control. Several worldwide reports have suggested that autologous transplantation of islet cells isolated from an unaffected portion of a resected pancreas, mostly for the cure of chronic pancreatitis or a pancreatic tumor without immunosuppressive agent treatment, resulted in good glycemic control, and even in the prevention of DM. Attempts were made to evaluate the effect of islet autotrans-plantation for glycemic control in eight patients undergoing a pancreatectomy for a benign pancreatic tumor. METHOD: Between December 2001 and October 2003, an islet autotransplantation was performed in eight patients patholologically confirmed with benign pancreatic tumors following a pancreatectomy. There was no past medical history of DM in any of the patients, but impaired glucose tolerance(IGT) was detected in 2 patients on a 75g oral glucose tolerance test(oral GTT), and was also suspected in a pre-pancreatectomy state patient. Islets were isolated by ductal perfusion, using the cold collagenase P and semi-automated method, and purified on a density gradients using a COBE 2991 cell processor or tube system of Ficoll solution. After being confirmed as a benign pancreatic tumor, the cultured islet cells were transplanted to the liver through the portal vein. Each patient was transplanted with a mean islet mass of 3,190+/-896 islet equivalents per kilogram of body weight. The median follow-up period was 12 months, with the longest being 36 months. All patients underwent follow-up for oral GTT, HbA1c and complication of DM, pancreatectomy, or transplantation within this period. RESULTS: On the 75g oral GTT, a normal glucose tolerance(NGT) was maintained until the last follow-up month in five of the eight patients undergoing islet autotransplantation. DM recurred in three of the eight patients undergoing islet autotransplantation, with to cases in a state of IGT and 1 case of NGT at the initial stage. The HbA1c levels were not significantly changed between pre-pancreatectomy and post-islet transplantation period. The amplitude of the decrease in the postprandial 2 hour glucose level was larger than that of the fasting glucose level between the pre- and post-transplantation periods, but this was not statistically. Also, the elevation of the postprandial C-peptide level was larger than the fasting C-peptide during the post-transplantation period, but again, this was not significant. No complications occurred in relation with the islet transplantation, portography, DM and hypoglycemia. CONCLUSION: Islet transplantation could prevent and reverse the diabetic process in patients undergoing a pancreatectomy for a benign pancreatic tumor, with some exception such as those with a small transplanted islet mass or with initial insulin resistance. The 2 hour postprandial changes in the glucose and C- peptide levels on the oral GTT somewhat reflected insulin secretory function of the remaining and newly transplanted islet cells. Pancreatic islet autotransplantation is the most prospective method for the prevention or cure of insulin deficient DM following a pancreatectomy for a benign pancreatic tumor.
- Relationship between C-peptide, Metabolic Control and Chronic Complications in Type 2 Diabetes.
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Jeung Mook Kang, Won Young Lee, Ji Youn Kim, Jung Won Yun, Sun Woo Kim
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Korean Diabetes J. 2002;26(6):490-499. Published online December 1, 2002
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- BACKGROUND
Type 2 diabetes mellitus is a heterogeneous disease characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production. As the decline of beta-cell function in type 2 diabetes is very slow, the relationship between the insulin secretory capacity, the degree of metabolic control and chronic complications is still unclear. The determination of plasma C-peptide allows for the assessment of the endogenous insulin production, even in the presence of exogenous insulin administration. The aim of this study was to evaluate the relationship between the serum C-peptide level and metabolic parameters, and the complications in type 2 diabetes. METHOD: The clinical characteristics and laboratory findings, such as lipid profile, fasting plasma glucose, HbA1C and uric acid, were evaluated, and their relationships with chronic complications analyzed. We measured the serum C-peptide level by radioimmunoassay (RIA) in 384 type 2 diabetes mellitus patients. The patients were divided into quartile groups according to their fasting C-peptide levels (quartile 1: <1.73 ng/mL, n=95; quartile 2:>or=1.73 ng/mL and <2.38 ng/mL, n=95; quartile 3:>or=2.38 ng/mL and <3.18 ng/mL, n=98; quartile 4:>or=3.18 ng/mL, n=96). RESULTS: Patients in the lowest C-peptide quartile showed significantly higher durations of diabetes, HbA1C and postprandial plasma glucose values, and HDL-cholesterol. Conversely, the BMI, systolic blood pressure, total cholesterol and triglyceride were significantly higher in the highest C-peptide quartile. The prevalence of diabetic retinopathy and urinary protein excretion were higher in lowest quartile, and the diastolic blood pressure was highest in the upper quartile, but these were not statistically significant. The associations between C-peptide, and the duration of diabetes, BMI, total cholesterol, triglyceride, HDL cholesterol, postprandial 2 plasma glucose and systolic blood pressure remained significant, even after multiple adjustments. CONCLUSION: In type 2 diabetes, higher C-peptide levels are associated with a component of metabolic syndrome and lower C-peptide levels due to decreased cell reserves, associated with hyperglycemia and microvascular complications
- Lipoprotein (a) Level and Vascular Complications in NIDDM.
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Ji Youn Kim, Mung Su Kim, Joung Min Kim, Jai Hong Park, Joung Hun Lee, Seung Won Yang, Dong Jin Chung, Min Young Chung, Tai Hee Lee
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Korean Diabetes J. 1998;22(1):65-73. Published online January 1, 2001
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Abstract
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- BACKGROUND
The risk of atherosclerosis is increased in subjects with diabetes mellitus. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic vascular disease in subjects without diabetes. The contribution of Lp(a) to the increased risk for atherosclerosis and diabetic complications in subjects with diabetes is not well known. In this report we examined the relationship between Lp(a) levels and development of vascular (macro- and microvascular) complications, and the relationship between Lp(a) and other risk factors for vascular complications in subjects with non-insulin-dependent diabetes mellitus(NIDDM), METHODS: For this study we evaluated 152 patients with NIDDM(72 women and 80 men). Lp(a) level was measured with N-Latex Lp(a) Reagent. Electrocardiography, coronary angiography, brain CT/MRI, doppler velocimetry and peripheral angiography were done for diagnosis of macravascular complieations, and fundus camera, nerve conduction velocity, BBV (beat to beat variation), VPT(vibration perception threshold) and 24-hour urine protein amount were examined for diagnosis of microvascular complications. RESULTS: Lp(a) levels in subjects with ischemic heart disease, cerebrovascular disease and diabetic retinopathy were significantly higher than those in subjects without above mentioned diseases. ApoB/ApoA1 ratio and LDL-cholesterol levels in subjects with Lp(a) level>30mg/dL were significantly higher than those in subjects with Lp(a) level 30mg/dL, and Lp(a) has a positive correlation with ApoB/ApoA1 ratio and LDL-cholesterol in NIDDM patients with vasculopathy. CONCLUSION: These results suggest that high Lp(a) levels seem to be associated with macrovascular and microvascular(especially with retinopathy) complications in subjects with NIDDM and Lp(a) level should be measured in the NIDDM with high level of ApoB/ApoA1 ratio and/or LDL-eholesterol.
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