Abnormality in molecular mechanism of cardiac -adrenergic signalling system and its usefulness in diabetes mellitus.
| Project/Area Number |
62570284
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Legal medicine
|
|---|
| Research Institution | Third Department of Medicine, Shiga University of Medical Science |
|---|
Principal Investigator |
ATSUNORI KASHIWAGI Third Department of Medicine, Shiga University of Medical Science, 医学部, 講師 (20127210)
|
|---|
| Project Period (FY) |
1987 – 1988
|
| Project Status |
Completed (Fiscal Year 1988)
|
| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Keywords | Diabetes Mellitus / Heart failure / Diabetic cardiomyopathy / -adrenergic receptor abnormality of adrenergic signalling system / Desensitization / 心不全 / 脱感作現象 / 糖尿病性心筋症 / β-アドレナリン受容体 / 脱感作現象糖尿慢性心筋症 |
|---|
| Research Abstract |
In order to evaluate the basic molecular mechanism of cardiac -adrenergic dysfunction in diabetes mellitus, we have measured -adrenergic (AD) signalling system in both isolated cardiac plasma membrane and cardiac myocytes in streptozocin (STZ)-induced diabetic rats.
A. DEFICIENCY OF CARDIAC -Ad RECEPTOR IN STREPTOZOCIN-INDUCED DIABETIC RATS.
1. The number of -Ad receptors on cardiac plasma membrane isolated from the diabetic rats was decreased by 50%, as compared with the control. 2. In the 10-wk-diabetic rats, the response of adenylate cyclase to isoproterenol was significantly defective (56% decrease), although both the basal and the forskolinstimulated maximum adenylate cyclase activities were similar in control and diabetic rats. 3. Both cholera toxin-dependent (Ns) and islet-activation proteindependent (Ni) [32P]NAD incorporations into cardiac plasma membrane were markedly increased in diabetic rats. B.ABNORMALITIES OF DISTRIBUTION OF CARDIAC -Ad RECEPTOR IN DIABETIC RATS. The diffe
… More
rential measurement of cell surface and total cell -Ad receptor concentrations was ecaluated by using isolated cardiac myocytes. Cell surface [3H]CGP-12177 binding sites in diabetic rats decreased by 41% without a difference in total cell receptor concentration. Forty eight hour in vivo insulin treatment significantly increased cell surface -Ad receptor concentration by 37% in diabetic rats without any change in total receptor concentration. C. MECHANISM OF A DEFICIENCY OF CARDIAC PLASMA MEMBRANE -Ad RECEPTOR IN DIABETIC RATS. Therer is a significant increase in cardiac -Ad receptor concentration in diabetic rats by incubating cells in the presence of phorbol ester. On the other hand, 10 isoproterenol-dependent decrease and the recovery of cell surface receptors after the removal of the agonist were significantly impaired in diabetic rats.
These results indicate that only cell surface -Ad receptor decreases in diabetic rats, thich may assoxiate with abnormalities in the receptor distribution. The decrease in cell surface receptor number closely associates with diabetic state and is reversed by the short-term insulin treatment. Less
|
Report
(3 results)
Research Products
(40 results)
-
-
-
-
-
[Publications] Nishio,Y.,;Kashiwagi,A.,;Kida,Y.,;Kodama,M.,;Abe,N.,;Saeki,Y.,;Shigeta,Y.: Diabetes. 37. 1181-1187 (1988)
Description
「研究成果報告書概要(和文)」より
Related Report
-
[Publications] Kashiwage,A.,;Nishio,Y.,;Saeki,Y.,;Kida,Y.,;Kodama,M.,;Shigeta,Y.: Diabetes. 37. 85A (1988)
Description
「研究成果報告書概要(和文)」より
Related Report
-
-
[Publications] Kashiwagi,A.,;Nishio,Y.,;Saeki,Y.,;Kida,Y.,;Kodama,M.,;Shigeta,Y.: Amer J Physiol. (1989)
Description
「研究成果報告書概要(和文)」より
Related Report
-
-
-
-
-
[Publications] Nishio,Y.,;Kashiwagi,A.,;Terada,M.,;Kida,Y.,;Hatanaka,I.,;Shigeta,Y.: "BEST APPROACH TO THE IDEAL THERAPY OF DIABETES MELLITUS" Excerpta Medica, 4 (1987)
Description
「研究成果報告書概要(和文)」より
Related Report
-
[Publications] Terada,M.,;Yasuda,H.,;Kashiwagi,A.,;Nishio,Y.,;Hatanaka,I.,;Yamashita,M.,;Miyamoto,Y.,;Kikkawa,R.,;Shigeta,Y.: "BEST APPROACH TO THE IDEAL THERAPY OF DIABETES MELLITUS" Excerpta Medica, 4 (1987)
Description
「研究成果報告書概要(和文)」より
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Publications] Terada,M.;Yasuda,H.;Kashiwagi,A.;Nishio,Y.;Hatanaka,I.;Yamashita,M.;Miyamoto,Y.;Kikkawa,R.;Shigeta,Y.: "BEST APPROACH TO THE IDEAL THERAPY OF DIABETES MELLITUS" Excerpta Medica, 4 (1987)
-
-
-
-
-
