| Project/Area Number |
63570531
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Shinshu University |
|---|
Principal Investigator |
AIZAWA Toru Shinshu University, School of medicine, Assistant Professor, 医学部, 講師 (90150896)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKASU Nobuyuki Shinshu University, School of Medicine, Associate Professor, 医学部, 助教授 (20020927)
|
|---|
| Project Period (FY) |
1988 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Keywords | Aging / Pancreatic B-cell / Diabetes Mellitus / Insulin / Intracellular signal Transduction / 労化 / GTP結合淡白 / カルシウムチャンネル / 細胞内カルシウム濃度 / インスリン分泌 / G蛋白 / 電位依存性カルシウムチャンネル / 細胞内遊離カルシウム |
|---|
| Research Abstract |
We investigated the mechanism of age-related B-cell disfunction from the view point of signal transduction using rats and the results addressed below indicate that the increase of NIDDM with aging in human is at least partly due to these abonormalities in the B-cell.
1. We found the existence of two two types of voltage dependent calcium channel and stimulatory GTP-binding protein coupled to insulin release in the intact rat B-cell. We also reported for the first time the elevation of cytosolic free calcium in response to glucose using whole pancreatic islets. The functional significance of these components in stimulated insulin release is elucidated as well. Accordingly, the ageーrelated changes of these pathways are studied as follows.
2. We found the first phase of glucose-stimulated insulin release is gradually delayed with aging. The delay is specific to the glucose-induced first phase response such that the second phase response to glucose, the responses to K^+ depolarization and arginine do not delay with aging. The elevation of cytosolic free calcium in response to glucose is not delayed in the islets of aged rats indicating the defect lies distal to the elevation of cytosolic free calcium and the derangement in ATP-sensitive K^+ channel independent pathway is suggested.
3. We found the sensitivity of the B-cell to glucose and dihydropyridine calcium channel blocker is lowered with aging. Also the responsiveness to the agonist of A-kinase and GTP-binding protein but not that to the PKC agonist is reduced with age. The data indicate than cyclic AMP-A kinase branch, the voltage dependent calcium channels and GTP-binding protein are likely to be altered with aging and forms the basis of age-related B-cell disfunction and glucose intolerance.
|
