| Project/Area Number |
10672071
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Meijo University |
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Principal Investigator |
MIWA Ichitomo Meijo University, Faculty of Pharmacy, Professor, 薬学部, 教授 (60076734)
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| Co-Investigator(Kenkyū-buntansha) |
TOYODA Yukiyasu Meijo University, Faculty of Pharmacy, Assistant Professor, 薬学部, 講師 (60103264)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | glucokinase / hepatic glucose metabolism / diabetes mellitus / regulation of metabolism / oral hypoglycemic drug / troglitazone / OLETFラット / GKラット |
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| Research Abstract |
We have recently found that glucokinase (GK ; one of the rate-limiting enzymes in the glycolytic pathway) translocates from the nucleus to the cytoplasm of primary cultures of rat hepatocytes when the cells are incubated with high concentrations (>10 mM) of glucose. We proposed that his translocation of GK might be involved in the regulation of hepatic glucose metabolism. The purpose of the present study was to get evidence for our proposal. Another purpose was to examine whether the derangement of GK translocation is implicated in the impairment of hepatic glucose metabolism in type 2 diabetes.
The results of the present study are shown below :
1. We developed a method for the quantitative estimation of cytoplasmic and nuclear GK in hepatocytes. By using the method, we demonstrated that the increase in the cytoplasmic GK is well correlated with that in the GK activity. This finding indicates that GK translocation is implicated in the regulation of hepatic glucose metabolism.
2. We found that the translocation of GK from the nucleus to the cytoplasm by high glucose is attenuated in hepatocytes from two type 2 diabetes model rats, Goto-Kakizaki rat and OLETF rat. This suggests that the attenuate GK translocation may be one of the cause of the impairment of hepatic glucose metabolism in type 2 diabetes.
3. During the course of the screening of compounds capable of stimulating the GK translocation, we found that troglitazone, an oral hypoglycemic drug, causes apoptosis of primary cultures of rat hepatocytes. It seems possible that this action of troglitazone is implicated in the well-known side effect, i.e.hepatic damage, of the drug.
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