| Project/Area Number |
04671482
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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 |
内分泌・代謝学
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| Research Institution | Yamaguchi University, School of Medicine |
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Principal Investigator |
INOUE Yasushi Yamaguchi University, School of Medicine, Assistant Professor, 医学部・附属病院, 助手 (10176448)
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| Co-Investigator(Kenkyū-buntansha) |
KAKU Kohei Yamaguchi University, School of Medicine, Assosiated Professor, 医学部, 助教授 (10116709)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Liver / Sulfonylurea / Glibenclamide / Tolbutamide / Fructose-2,6-bisphosphate / Phosphenolpyruvate carboxykinase / Glycolysis / Gluconeogenesis / スルフォニル尿素剤 / フォスフォエノールピルビン酸カルボキシナーゼ / スルフォニルウレア / CS-045 / PEPCK |
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| Research Abstract |
1) Demonstration of the specific binding sites fo glibenclamide in rat liver membrane. The characters of the binding sites for [^3H]glibenclamide in rat crude liver membrane fraction were analyzed. The binding was specific, time- and temperature-dependent, and reversible. The calculated dissociation constant (Kd=1.1muM) was higher that those reported in beta-cell tumors or brain. The binding sites in the liver, however, seemed to play some roles because the stimulation of fructose-2,6-bisphosphate (F-2,6-P_2) production and inhibition of phosphoenolpyruvate carboxykinase (PEPCK) were observed in these concentrations of sulfonylurea(SU) drugs.
2) Non-SU anti-diabetic drug, CS-045, has no stimulatory effect on insulin secretion from the beta-cells. The hypoglycemic effect should be based on "extra-pancreatic" action. We demonstrated that CS-045 stimulates F-2,6-P_2 production by the similar mechanism to tolbutamide. The fact may suggest that CS-045 reduces blood glucose by facilitating glycolysis in the liver.
3) We showed that tolbutamide inhibits the activity of PEPCK, the key enzyme in gluconeogenesis, in rat hepatoma cell line H4-IIE cells. The inhibition is caused by reduction of mRNA for PEPCK in the cells.
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