1992 Fiscal Year Final Research Report Summary
Physiological and molecular biological studies on altered function of the intracellular signal transduction system in pancreatic beta cells of diabetes mellitus.
| Project/Area Number |
03671145
|
|---|
| 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 | KYOTO UNIVERSITY |
|---|
Principal Investigator |
ISHIDA Hitoshi Assistant Professor, Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, 医学部, 助手 (80212893)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUDA Kinsuke Associate Professor, Department of Integrated Human Sciences, Kyoto University, 総合人間学部, 助教授 (10180001)
SEINO Yutaka Associate Professor, Department of Metabolism and Clinical Nutrition, Kyoto Univ, 医学部, 助教授 (40030986)
|
|---|
| Project Period (FY) |
1991 – 1992
|
| Keywords | Diabetes mellitus / Intracellular signal transduction system / Intracellular calcium concentration / insulin / ATP-sensitive K^+ channel / Voltage-dependent Ca^<2+> channel / Patch-clamp technique |
|---|
| Research Abstract |
In order to elucidate the intracellular mechanisms of impaired insulin secretion induced by glucose from pancreatic beta cells in diabetes mellitus, the altered functions of intracellular calcium signaling system and ion channels were investigated using beta cells obtained from rats of experimentally-induced non-insulin-dependent diabetes mellitus (NIDDM), or those exposed to high glucose in vitro. The glucose-induced insulin release is significantly reduced in these cells compared to the controls. In addition, the intracellular calcium ([Ca^<2+>]i) response is similarly decreased after the glucose loading. These facts clearly indicate that the abnormalities in intracellular calcium signaling system in beta cells is closely related to the impaired insulin secretion induced by glucose in NIDDM. To further elucidate the pathogenesis of reduced [Ca^<2+>]i response, the properties of ATP sensitive K^+ channel (K_<ATP> channel) was studied in NIDDM rats using the patch-clamp technique. The inhibitory effect of glucose on beta cell K_<ATP> channel activities is significantly impaired in NIDDM rats compared to the controls, but the ATP sensitivity is identical between them. The glucose insensitivity of K_<ATP> channels is, therefore, probably due to an insufficient ATP production caused by impaired glucose metabolism in beta cells of NIDDM. The insufficient depolarization of beta cell plasma membrane due to the reduced inhibition of K_<ATP> channel activities seems to cause the decreased [Ca^<2+>]i elevation in NIDDM beta cells, leading to the impaired isulin secretion induced by glucose.
|
-
-
-
-
-
-
-
-
-
[Publications] T.Kurose, K.Tsuda, H.Ishida, K.Tsuji, Y.Okamoto, Y.Tsuura, S.Kato, M.Usami, H.Imura, Y.Seino: "Glucagon, insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats." Diabetologia. 35. 1035-1041 (1992)
Description
「研究成果報告書概要(欧文)」より
-
-
-
