| Project/Area Number |
10671080
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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 |
Metabolomics
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| Research Institution | KAGOSHIMA UNIVERSITY |
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Principal Investigator |
KAKEI Masafumi KAGOSHIMA UNIVERSITY, UNIVERSITY HOSPITAL, INTERNAL MEDICINE, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (90214270)
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| Co-Investigator(Kenkyū-buntansha) |
YADA Toshihiko KAGOSHIMA UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF PHYSIOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (60166527)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | K-ATP CHANNEL / SULFONYLUREA / INSULIN SECRETION / PANCREATIC B-CELLS / PIP2 / SUR / KIR / Kir / イオンチャネル / 糖尿病 / スルフォニル尿素薬 / β細胞 |
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| Research Abstract |
ATP-sensitive KィイD1+ィエD1 channels play an important role in the glucose-stimulated insulin secretion in pancreatic β-cells. The channel determine the resting membrane potential of β-cells and closure of the channel is the first event appeared in glucose-stimulated β-cells. It has been established that sulfonylureas initiate the insulin secretion as a result of closure of the K-ATP channel by binding to their receptor. The channel is composed of sulfonylureas receptor, SUR, and inwardly rectifying channel, Kir6.2. We studied a mechanism underlying signal transduction from the SUR to Kir6.2 and following results were obtained.
(1) Tolbutamde (SU) inhibited the ATP-sensitive KィイD1+ィエD1 channels. The sensitivity of the channel to tolburtamide was reduced after the treatment of the channel with 2 μM CaィイD12+ィエD1.
(2) At this time, the increasing effect of ADP on the channel activity disappeared.
(3) The sensitivity of the channel to ATP was kept normal.
(4) PIP2, membrane phospholipid, prevented the loss of tolbutamide sensitivity induced by CaィイD12+ィエD1.
(5) From these results, we suggest that CaィイD12+ィエD1 may influence the channel protein by decreasing the sensitivity to tolbutamide and ADP. PIP2 may be reduced by the treatment with high CaィイD12+ィエD1. These may interfarewith the signalling from SUR to Kir6.2 and PIP2 my be required for maintaining the signalling between both subunits.
(6) It has been known that the channel similar to b-cell type K-ATP channel is expressed in the myocardial cells. When PIP2 was decerased by exposure of cells to extracellular ATP, the K-ATP channel current was decreased.
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