Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells

被引：36

作者：

Damdindorj, Boldbaatar ^{[1
]}

Dezaki, Katsuya ^{[1
]}

Kurashina, Tomoyuki ^{[1
]}

Sone, Hideyuki ^{[1
]}

Rita, Rauza ^{[1
]}

Kakei, Masafumi ^{[2
]}

Yada, Toshihiko ^{[1
]}

机构：

[1] Jichi Med Univ, Div Integrat Physiol, Dept Physiol, Sch Med, Shimotsuke, Tochigi 3290498, Japan

[2] Jichi Med Univ, Dept Med 1, Saitama Med Ctr, Sch Med, Saitama 3378503, Japan

来源：

FEBS LETTERS | 2012年 / 586卷 / 16期

基金：

日本学术振兴会;

关键词：

Ghrelin; GLP-1; Insulin release; Cytosolic Ca2+; cAMP; Islet beta-cell; GLUCAGON-LIKE PEPTIDE-1; GLUCOSE-TOLERANCE; PANCREATIC-ISLETS; RECEPTOR; ACYLTRANSFERASE; EXPRESSION; RELEASE; TYPE-2; IDENTIFICATION; CA2+;

D O I：

10.1016/j.febslet.2012.06.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We studied interactive effects of insulinotropic GLP-1 and insulinostatic ghrelin on rat pancreatic islets. GLP-1 potentiated glucose-induced insulin release and cAMP production in isolated islets and [Ca2+](i) increases in single beta-cells, and these potentiations were attenuated by ghrelin. Ghrelin suppressed [Ca2+](i) responses to an adenylate cyclase activator forskolin. Moreover, GLP-1-induced insulin release and cAMP production were markedly enhanced by [D-lys(3)]-GHRP-6, a ghrelin receptor antagonist, in isolated islets. These results indicate that both exogenous and endogenous islet-derived ghrelin counteracts glucose-dependent GLP-1 action to increase cAMP production, [Ca2+](i) and insulin release in islet beta-cells, positioning ghrelin as a modulator of insulinotropic GLP-1. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：2555 / 2562

页数：8

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