Study on the mechanism of insulin action on glucose transport
| Project/Area Number |
05670837
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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 | Gunma University Institute For Molecular and Cellular Regulation |
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Principal Investigator |
SHIBATA Hiroshi Gunma University, Institute for Molecular and Cellular Regulation, Department of Cell Biology, lecturer, 生体調節研究所, 講師 (20235584)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | insulin / glucose transporter / G-protein |
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| Research Abstract |
Effects of guanine nucleotides on either exocytosis or endocytosis of GLUT4 were examined in electrically permeabilized rat adipocytes by using D^k- (62-85), a MHC class l-derived peptide. Reversal of glucose transport activity which had been stimulated with insulin was completely blocked and the activity was rather enhanced 25% in the presence of D^k- (62-85), indicating that the peptide blocked endocytosis of GLUT4. In agreement with this notion, endocytosis of trypsin-cleaved 35 kDa fragment of GLUT4 was almost completely inhibited by the peptide. Therefore, in the presence of the peptide, exclusively exocytotic accumulation of GLUT4 on the cell surface could be measured. Insulin-stimulated glucose transport activity was enhanced about 50% in the presence of D^k- (62-85) while the basal transport activity was stimulated only slightly. Although GTP_<gamma>S augmented glucose transport to the same extent as insulin in the absence of D^k- (62-85), GTPgS-stimulated glucose transport was only 60% of the insulin effect in the presence of the peptide : the effects of insulin was markedly enhanced by the peptide whereas glucose transport induced by GTPgammaS was not affected, suggesting that GTP_<gamma>S has a similar effect to the peptide. In fact, endocytosis of 35kDa fragment of GLUT4 was markedly inhibited by GTPgammaS.In addition, GLUT4 endocytosis was accelerated by GTP but was inhibited by GDPbetaS.These results indicate that GTPgammaS induces translocation of GLUT4 by both stimulating exocytosis and inhibiting endocytosis. Distinct types of GTP-binding proteins are involved in exocytosis and endocytosis of GLUT4.
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Report
(3 results)
Research Products
(3 results)
