- Insulin Gene Therapy using Vascular Smooth Muscle Cells in Diabetic Rats.
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Tae Geun Oh, Mi Ja Lee, Young Ku Kim, Seung Tak Kim
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Korean Diabetes J. 2002;26(1):32-46. Published online February 1, 2002
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 Abstract
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- BACKGROUND
Type 1 diabetes mellitus is caused by a lack of insulin. The purpose of this study was to test whether blood glucose control in severe diabetic animals can be achieved by transplanting of rat vascular smooth muscle cells which are transduced with the insulin gene using a retroviral vector system. METHODS: After cloning the recombinant retroviral plasmid including human mutated proinsulin cDNA which contains furin endopeptidase cleavage site, the resulting plasmid, LInABCSN, was transfected into the retroviral packaging cell line (PA317/LhInABCSN). The resulting retrovirus in the supernatant of PA317/ LhInABCSN infected the F344 rat vascular smooth muscle cell (SMC) and produced the SMC/LhInABCSN cells. After transplanting SMC/LInABCSN cells into the internal carotid artery of the rat, diabetes was induced by an intraperitoneal streptozotocin (STZ) injection (50 mg/kg) 2 week later. The blood glucose and insulin levels, percent weight change and the survival rates between the control group (SMC/LNFZ) and the treatment group (SMC/LInABCSN) were compared. RESULTS: The insulin concentrations in the supernatant of the SMC/LhInABCSN mice were 160.2 IU/mL in 24 hours, 243.6 IU/mL in 48 hours and 350.2 IU/mL in 72 hours, but the proinsulin concentrations in 24, 48 and 72 hours were all lower than 1 pmol/L. After 1 day and 3 days of the STZ injection, there were no differences in glucose concentrations between treatment group (n=10) and control group (n=10). There were no statistical differences in the percent weight change between the control and treatment group but the treated rats showed bad a lower weight loss than control rats. After 3 days of the STZ injection, serum insulin concentration of treatment group showed slightly higher levels than the control group (2.7+/-.5 IU/mL vs. 1.6+/-.1 IU/mL, p=0.077). The survival showed a significant increase in treatment group (median survival: 29 days, 9-104 days) compared to the control group (median survival: 6 days, 3-49 days, p < 0.05). CONCLUSION: Although this study did not show a normal glucose concentration in treated rats, it did show significantly higher survival compared to control rats. It is believed that gene therapy using rat vascular smooth muscle cells which transduced the insulin gene may be a new insulin delivery method.
- Comparison of the Antiproteinuric Effect to ACE Inhibitors in NIDDM Patients with Nephropathy According to Genotypes of ACE Gene.
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Yong Mo Yang, Jeong Chul Seo, Kyoung Soo Lee, Won Joong Jeon, Hyun Hee Lee, Ji Bong Jeong, Seong Su Koong, Tae Geun Oh
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Korean Diabetes J. 2000;24(4):476-484. Published online January 1, 2001
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Abstract
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- BACKGROUND
Albuminuria is a risk factor for progression of diabetic nephropathy. Antihypertensive treatment, especially angiotensin converting enzyme (ACE) inhibition, has been shown to reduce albuminuria and to ameliorate progression of diabetic nephropathy in IDDM patients. Recently, an insertion (I)/deletion (D) polymorphism of the ACE gene (ACE/ID) has been shown to influence the antiproteinuric efficacy of ACE inhibition in non-diabetic renal disease and the deterioration in kidney function in both non-diabetic and diabetic kidney disease. We evaluated the potential role of the ACE/ID polymorphism on the antiproteinuric responsiveness to ACE inhibition in NIDDM patients with nephropathy. METHODS: 35 NIDDM patients with overt proteinuria were included in this study. DNA amplified by PCR techniques was used to detect the two alleles of the ID polymorphism. Subjects were classified as II+ID group and DD group according to the presence (I) or absence (D) of a 270 base pair insertion. Ramipril was used for ACE inhibition. At a baseline and an end of the study(6 months later from baseline), arterial blood pressure, HbA1c, serum creatinine, creatinine clearance, and 24 hour urine protein amount were measured. The significant response to ACE inhibition was defined as a decline in proteinuria > or =30% of baseline. RESULTS: The MABP was decreased significantly in each groups, but the degree of BP reduction was not different between the groups. Twenty-four hour urine protein amount and creatinine clearance was not different in each groups and between CONCLUSION: Antiproteinuric effect of ACE inhibition was not associated with ACE/ID polymorphism in diabetic patients with nephropathy.
- Relationship between Angiotensin I Converting Enzyme Gene Polymorphism and Vascular complications in Non-Insulin Dependent Diabetic Patients.
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Byoung Gue Na, Tae Geun Oh, Sang Moo Jung, Sang Woo Oh, Jae Hong Choi, Ji Hyun Lee, Seong Su Koong, Seung Taik Kim
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Korean Diabetes J. 1997;21(2):138-146. Published online January 1, 2001
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- No abstract available.
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