1990 Fiscal Year Final Research Report Summary
New Aspects on the Mechanism of Streptozotocin-Induced Diabetes : Role of Xanthine Oxidase
| Project/Area Number |
01571212
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Tokushima |
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Principal Investigator |
KAWADA Jun University of Tokushima, Professor, 薬学部, 教授 (10035537)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Yoshiyuki University of Tokushima, Assistant Prof., 薬学部, 助手 (20035554)
NISHIDA Mikio University of Tokushima, Associate Prof., 薬学部, 助教授 (10035561)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Allopurinol / ATP / NAD / Insulin / Pancreatic beta cell / Mitochondria / Xanthine oxidase / Free radicals |
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| Research Abstract |
Isolated rat pancreatic beta cells were shown to be protected from the cytotoxic effect of streptozotocin (SZ) by allopurinol. Pretreatment with allopurinol for 2 h caused dosedependent inhibition of the decreased secretion of insulin by the cells induced by SZ pretreatment with allopurinol also preevented the rapid decrease in intracellular ATP and Nad concentrations in beta cells induced by treatment with SZ high performance liquid chromatography revealed that the intracellular concentration of uric acid in SZ-treated cells was about 3 fold that of control cells. This finding suggests that the reaction of xanthine oxidase is facilitated in the cells exposed to SZ probably due to an increased supply of substrate resulting from decrease in intracellular ATP.
Streprozotocin decreased oxygen consumption of rat liver mitochondria in a time-and dose-dependent manner and enhanced the generation of hydroxyl radicals (DMPO-adducts). This enhancement was doubled on the addition of succinate as a substrate. Mitochondrial ATP generation was also decreased significantly by SZ thus the marked depletion of intracellular ATP in beta cells by SZ seems to be due mainly to a direct effect on mitochondrial production. From these results, we suggest that the cytotoxic effect of SZ in pancreatic beta cells is due to a reduction in the intracellular level of ATP, rat her than of NAD.
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