- Insulin Gene Therapy Using HVJ-liposome and Epstein-Barr Virus Plasmid in Murine Streptozotocin Induced Diabetes.
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Yong Deuk Kim, Keun Gyu Park, Seong Wook Han, Jong Doek Ahn, Hyo Jung Lee, Mi Jung Kim, Hye Soon Kim, Nam Hee Park, In Kyu Lee
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Korean Diabetes J. 2003;27(5):405-413. Published online October 1, 2003
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- BACKGROUND
Despite improvement in insulin preparation and delivery, the use of insulin therapy alone to maintain normal glucose concentration and prevent the development of diabetic complication is not easy. Therefore, there has been considerable interest in developing gene therapy to supply insulin. We investigated that the administration of hemagglutinating virus of Japan (HVJ)- liposome complex, containing human insulin construct into the portal vein to control the blood glucose level in murine streptozotocin (STZ)-induced diabetes. METHODS: Human insulin gene was delivered to STZ-induced diabetic rats through the portal vein using HVJ-liposome containing Epstein-Barr virus (EBV) replicon-based plasmid (pEB). Blood glucose and body weight were measured after insulin gene delivery. The animals were sacrificed 28 days later and the livers were collected for immuno-histochemical staining of insulin. In addition plasma insulin and C-peptide levels were measured. RESULTS: Significant decrease in blood glucose levels and an increase in insulin and C-peptide levels were observed in the insulin gene transfection group as compared to the control group. Immunohistochemical staining of insulin also showed significant differences between these two groups. CONCLUSION: This study demonstrated the possibility of insulin gene therapy through the portal vein using pEB and HVJ-liposome method to produce a sustained improvement of diabetic glucose metabolism.
- The Effect of alpha-lipoic Acid on Endothelial Dysfunction Induced by Intralipid Infusion in Healthy Volunteers.
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Dong Wook Lee, Mi Jung Kim, Hye Soon Kim, Tae Sung Yun, Ho Chan Cho, Sang Jun Lee, Seung Ho Hur, Kyo Cheol Mun, Yong Won Cho, Jae Hoon Bae, In Kyu Lee
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Korean Diabetes J. 2002;26(5):336-346. Published online October 1, 2002
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- BACKGROUND
Endothelial dysfunciton has been proposed as an early manifestation of atherogenesis. Recently, emerging evidence suggests that hypertriglyceridemia and elevated free fatty acid are important risk factors in the development of atherosclerosis, probably through an increased oxidative stress. To clarify the hypothesis, we evaluated the effect of alpha-lipoic acid (ALA) on the endothelial dysfunction induced by intralipid infusion in healthy volunteers. METHODS: Hypertriglyceridemia and elevated free fatty acids was induced by infusion of intralipid. FMD (Flow-mediated dilation) of the brachial artery was investigated noninvasively by a high-resolution ultrasound technique in 13 young, healthy men without risk factors for coronary heart disease. RESULTS: Plasma triglyceride, free fatty acid and the superoxide anion were increased from 61.7+/-28.8 to 332.6+/-202.5 mg/dL, from 330.7+/-131.1 to 1267.0+/-486.2 microEq/L and from 6.6+/-2.2 to 8.7+/-1.5 X 10(-7)nmol/10(6)cells/30min (vs. basal p<0.001), respectively, following infusion of the intralipid. The FMD was decreased from 10.1+/-3.3 to 7.7+/-3.7% (vs. basal p<0.01) following infusion of the intralipid. After treatment with ALA, the increase in the FMD and the decrease in superoxide anion were significant. CONCLUSION: Acute hypertriglyceridemia, induced by intralipid infusion, is implicated in endothelial dysfunction. This endothelial dysfunction was reversed by treatment with ALA. These results suggest that chronic and repeated hypertriglyceridemia may play important roles in the development of atherosclerosis probably by increasing oxidative stress.
- The Effect of Alpha-lipoic Acid on Endothelial Dysfunction in Postmenopausal Uncomplicated Type 2 Diabetes.
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Ho Chan Cho, Sang Jun Lee, Mi Jung Kim, Hye Sun Kim, Tae Sung Yun, Sung Jae Kim, Sang Hyon Kim, Seung Ho Hur, Kyo Chul Moon, Jae Hoon Bae, In Kyu Lee
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Korean Diabetes J. 2002;26(4):242-252. Published online August 1, 2002
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- BACKGROUND
Recently, increased oxidative stress has been proposed as a major cause of vascular complications of patients with diabetes mellitus. Increased generation of oxygen free radicals in patients with diabetes mellitus could deplete cellular antioxidants and inactivate endothelial dependent vasodilating factor (EDRF), such as nitric oxide (NO). The purpose of this study was to evaluate whether the antioxidant alpha-lipoic acid (ALA) is effective in endothelial dysfunction of brachial artery, which induced by increased oxidative stress in postmenopausal diabetic women using high resolution ultrasound technique and initial reaction time (IRT) measurement. METHODS: We enrolled 11 menopausal women (mean age, 56.5+/-5.1 years) with uncomplicated type 2 diabetes. All patients were taking 1200 mg of ALA (Thioctacid(R), Bukwang, Korea). We measured of superoxide anion (O2-) in neutrophils as a marker of oxidative stress. Flow-mediated dilation (FMD) was measured using a high-resolution ultrasound. RESULTS: After treatment of ALA, fasting blood glucose was decreased significantly, the endothelium-dependent vasodilation of the brachial artery was increased, and O2- production was also decreased significantly. CONCLUSION: These results show that short term ALA treatment could improve the endothelial dysfunction in patients with type 2 diabetes mellitus. This improvement might be related with the antioxidants effect of ALA.
- Effect of Self-monitoring of Blood Glucose on Pregnancy Outcome in Women with Mild Gestational Diabetes.
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Hak Chul Jang, Jeong Eun Park, Chang Hoon Yim, Ho Yeun Chung, Ki Ok Han, Hyun Koo Yoon, In Kwon Han, Moon Young Kim, Jae Hyug Yang, Mi Jung Kim, Sun Young Ko, Yeon Kyung Lee
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Korean Diabetes J. 2001;25(1):93-102. Published online February 1, 2001
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Self-monitoring of blood glucose (SMBG) and intensive therapy with insulin demonstrated to have a positive effects in the reduction of the neonatal complications in women with gestational diabetes (GDM). However the utility of SMBG in the mild GDM who does not requiring insulin has not been formally reported. Therefore, to evaluate the effectiveness of SMBG in the management of mild GDM, we compared the pregnancy outcome and the postpartum glucose tolerance of women who monitored their glycemic control by SMBG to those of women who monitored by laboratory glucose test at each office visit during pregnancy. METHODS: We studied 185 women diagnosed as a GDM by NDDG criteria and their fasting glucose concentration < 5.8 mM. All subjects had singleton pregnancy,and no medical diseases that may affect fetal growth, and were certain of gestational age by early ultrasonography. They were treated with an identical GDM management protocol except glucose monitoring. One hundred five women were monitored by laboratory glucose test at each office visit (office group) and 80 women were monitored by SMBG (SMBG group). Pregnancy outcome including rates of cesarian section, obstetric complication, LGA infant and glucose tolerance status at postpartum were compared between two groups. RESULTS: The age, height, prepregnancy weight, weight at delivery and parity were not significantly different between the two groups. Fasting, 1-h, 2-h glucose concentration during the diagnostic test of GDM in SMBG group were similar to those of office group. However, 3-h glucose concentration of office group was 0.3 mM higher than that of SMBG group. The rate of primary cesarian section, preterm labor and pregnancy-induced hypertension of SMBG group were similar to those of office group. The mean postprandial 2-h glucose concentration of office group measured at each office was 0.5 mM higher than that of SMBG group. Although 5% of office group were treated with insulin, 24% of SMBG group were requiring insulin therapy. The birth weight and LGA infant rate of office group were 3403 432 g and 28%, those were heavier and higher than those of SMBG group (3169 447 g, 13.8%). The 90% of office group and 84% of SMBG group were performed 75 g oral glucose tolerance test at postpartum 6-8 weeks. There was no significant difference in rates of diabetes and IGT between office and SMBG group (9.5%, 11.6%; 7.5%, 9.0% respectively). CONCLUSIONS: This study demonstrated that SMBG is very seful in early detection of maternal hyperglycemia and lowing the postprandial glucose, as well as reducing the rate of LGA infants in women with mild GDM.
- Spontaneous diabetes mellitus in the BB rat: effect of depletion ofT lymphocytes and natural killer cells on anti-islet cellular cytotoxicity.
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Ki Up Lee, Jin Hee Kim, Hae Sun Park, Gon Sup Kim, Mi Jung Kim
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Korean Diabetes J. 1992;16(3):199-203. Published online January 1, 2001
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- No abstract available.
- Spontaneous diabetes mellitus in the BB rat: anti-islet cellular cytotoxicity and natural killer (NK) cell activity.
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Ki Up Lee, Hae Sun Park, Mi Jung Kim
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Korean Diabetes J. 1992;16(1):1-7. Published online January 1, 2001
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- No abstract available.
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