The Role and Activation Mechanism of Phospholipase C in Insulin Secretion
| Project/Area Number |
61570548
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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 | Kyoto University |
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Principal Investigator |
TAMINATO Tomohiko Department of Medicine, Kyoto University, 医学部, 助手 (90107954)
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| Co-Investigator(Kenkyū-buntansha) |
SEINO Yutaka Department of Medicine, Kyoto university, 医学部, 助教授 (40030986)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1986: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Insulin Secretion / Pancreatic Islet / GTP-Binding Protein / Phospholipase C / イノシトールリン酸 / Cキナーゼ / インスリン分泌 / Isiet-Activating protein(IAP) / Inosital1,4,5-trisphosphate / 刺激伝達機構 |
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| Research Abstract |
Both diacylglycerol (DG) and inositol-1,4,5-trisphosphate (InsP3) have been shown to be key factors regulating stimulus transmission in the insulin secretion. In order to elucidate the activating mechanism of phospholipase C (PLC) which produces DG and InsP3, in vitro studies using isolated pancreatic islets of rats were performed. Islets were prelabeled with ^3H-myo-inositol and exposed to glucose (16.7 mM), carbachol (10 uM), arginine (10 mM), or <alpha>-ketoisocaproic acid ( KIC:10 mM) for 15 min followed by the treatment of CH3Cl/CH3OH (2/1). Lipid and water-soluble fractions were separated and InsP3 fraction was collected through a Dawex AGlX8 column.The ratio of InsP3/Lipid fraction was calculated as a function of PLC activity. Glucose, carbochol and arginine stimulated PLC activity. Neomycin (20-500 uM), a blocker of PLC, inhibited both insulin secretion and PLC activity stimulated by these agents dose-dependently. GTPrS (100 uM), an analogue of GTP, elicited insulin release when applied to the islet permeabilizedby ATP. GTPrS-stimulated insulin secretion and PLC activation were also suppressed by neomycin. Treatment of the islet with Islet-activating protein (IAP), an extract of pertussis foxin, augmented the effects of glucose on PLC and insulin secretion, but suppressed those induced by carbachol, arginine, or <alpha>-KIC.
These results suggest an important role of PLC and its agonist-specific coupling with the GTP-binding protein(s) in the pancreatic B cell.
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Report
(2 results)
Research Products
(10 results)
