Project/Area Number |
05454315
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
内分泌・代謝学
|
Research Institution | Gunma University |
Principal Investigator |
KOJIMA Itaru Professer, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, 生体調節研究所, 教授 (60143492)
|
Co-Investigator(Kenkyū-buntansha) |
SHIBATA Hiroshi Associate Professor, ibid., 生体調節研究所, 助教授 (20235584)
|
Project Period (FY) |
1993 – 1995
|
Project Status |
Completed (Fiscal Year 1995)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥3,200,000 (Direct Cost: ¥3,200,000)
|
Keywords | TGF-beta / activin A / pancreatic endocrine cell / differentiation / insulin / calcium / autocrine / paracrine / パラクリン機構 / オートクリン機構 / 局所因子 / 分化誘導因子 / 増殖因子 |
Research Abstract |
In the present research, we studied the role of members of TGF-beta supergene family in the regulation of pancreatic endocrine cell. We obtained the following results. First, we showed that activin A and TGF-beta are expressed in non-beta and beta-cells of the pancreatic islet, reapectively. Second, both activin A and TGF-beta stimulate insulin secretion by calcium-dependent manners. Furthermore, these two ligands inhibit the activity of the ATP-sensitive potassium channel and increase calcium influx via voltage-dependent calcium channel. This mode of action resembles that of glucose, a major stimulant of insulin secretion. Third, activin A is expressed in endocrine precursor cells found in pancreatic anlage and is thought to play a role in the differentiation of pancreatic endocrine cells. Consistent with this notion, activin A converted amylase-containing pancreatic AR42J cells, a cell line possessing characteristics similar to pancreatic precursor cells, into neuron-like cells. Furthermore, activin A-treated AR42J cells express pancreatic polypeptide, a pancreatic hormone. Hence, activin A converts AR42J cells into endocrine cells in pancreas.
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