| Project/Area Number |
09671038
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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 |
内分泌・代謝学
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
AIZAWA Toru SHINSHU UNIVERSITY Department of Geriatrics Associate Professor, 医学部, 助教授 (90150896)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAUCHI Keishi SHINSHU UNIVERSITY Department of Geriatrics Assistant Professor, 医学部, 講師 (30191191)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Pancreatic β cell / Insulin / Glucose Toxicity / Signal Transduction / Diabetes Mellitus / インスリン分泌 / 刺激・分泌連関 |
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| Research Abstract |
We have extensively analyzed molecular basis of glucose signaling in the pancreatic β cell. In relation to glucose toxicity, high plasma glucose was in fact priming the β cell and amelioration of hyperglycemia resulted in β cell suppression rather than β cell recovery. The finding indicates that high glucose primes the β cell under a certain circumstance. We can see β cell glucose toxicity in patients with 'ketosis-onset diabetes and subsequent non-insulin-dependency', which was established as a distinctive clinical entity by us. Characteristics of β cell glucose signaling in mouse with targeted disruption of IRS-1, glucokinase, and mGPDH was delineated. Regarding mediators of KATP channel-independent glucose action, synergism between signals arising from upper glycolytic pathway and mitochondrial metabolism was demonstrated. Furthermore, importance of lipid signal/protein acylation was discovered. Taken together, we reached to a working hypothesis that glucose stimulation of pancreatic β cell is mediated by 'not one but many' signals working in synergy.
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