| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
In the first year, whether hyperglycemia and hyperinsulinemia in Wistar Fatty rats are associated with disturbed expression of glucokinase(GK), 6phosphofructo-2-kinae(PFK2) and PEPCK genes was examined. Either activities or mRNA levels of GK, PFK2 and PEPCK were not significantly different between Wistar Fatty rats and their littermates, Witar Lean rats. Next, the effects of AD-4833, which, reportedly, enhances the insulin response, on the expression of GK, PFK2 and PEPCK genes in liver, and intermediates levels in blood were studied in Wistar Fatty rats. AD-4833 treatment resulted in the decrease of blood sugar and insulin levels, but expression of GK, PFK2 and PEPCK genes was not changed. In contrast, intermediate levels were affected by this drug. Glycerol levels were decreased, and lactate and pyruvate levels were increased. Taken these, the mechanisms to cause hyperglycemia in Wistar Fatty rats do not seem to be gene defects ofk GK, PFK2 or PEPCK.Mechanisms of AD-4833 do not seem to be the effects on these enzymes, either. In the next year, the effect of AD-4833 on the insulin-stimulated glucose transport activity in adipocytes isolated from Wistar Fatty rats was studied. This experiment is still in progress. Human genetic factors to cause NIDDM were also sutdied in pararell with the study in animal model. Islet promotor region was studied regarding the association with NIDDM.Consequently, sequence variants were found, which resulted in defects of promotor activities. The physiological significance of this promotor variants are now being studied. The possibilitiy of GK promotor defect as the cause of hyperglycemia in Wistar Fatty rats are also planned to be studied.
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