2000 Fiscal Year Final Research Report Summary
Reconstruction of pancreatic beta cell in non-islet cell -Analysis of signal transduction in first phase of insulin secretion
| Project/Area Number |
11671130
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | KUMAMOTO UNIVERSITY |
|---|
Principal Investigator |
MIYAMURA Nobuhiro KUMAMOTO UNIVERSITY MEDICAL SCHOOL RESEARCH ASSISTANT, 医学部・附属病院, 助手 (40274716)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SASAHARA Takayuki KUMAMOTO UNIVERSITY MEDICAL SCHOOL RESEARCH ASSISTANT, 医学部, 助手 (20304991)
SHIROTANI Tetsuya KUMAMOTO UNIVERSITY MEDICAL SCHOOL LECTURER, 医学部, 講師 (30274715)
KISIKAWA Hideki HEALTH CARE CENTOR PROFESSOR, 保健管理センター, 教授 (30161441)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Keywords | NON-ISLETS CELL / GLUT2 / GLUCOKINASE / PHOSPHOLIPASE C / K±ATP CHANNEL / VDCC / IP3 RECEPTOR |
|---|
| Research Abstract |
U73122, an inhibitor of phospholipase C, suppressed glucose-induced insulin secretion from isolated rat islets or mouse insulinoma MIN6 cells in static condition. In perifusion study, however, U73122 suppressed second phase of glucose-induced insulin secretion from rat islets. Although acute suppression of insulin release from rat islets was observed after negative stepwise glucose stimulation, delayed suppression was observed in case of MIN6 cells or AtT20HI-GLUT2-GK cells. Expression of two isoforms of phospholipase C (PLCβ, PLCγ) was observed in rat islets, MIN6 cells and AtT20HI-GLUT2-GK cells. Expression of PLCδ was observed in rat islets and MIN6 cells, but not in AtT20HI-GLUT2-GK cells. Furthermore, expression of type III inositol-1,4,5-triphosphate receptor was not observed in AtT20HI-GLUT2-GK cells. These data suggested that transfection of at least two genes coding PLCδ and type III IP3 receptor was required to reconstruct physiological insulin secretion machinery. Blockade of ATP-sensitive potassium channel (K^+ATP) or activation of voltage-dependent calcium channel (VDCC) induced insulin secretion from AtT20HI-GLUT2-GK cells. Opening of K^+ATP or blockade of VDCC suppressed glucose-induced insulin secretion from the cells. These indicated functional K^+ATP and VDCC were expressed in AtT20HI-GLUT2-GK cells.
|
