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

共 44 条

[1] Modulation of Ghrelin O-Acyltransferase Expression in Pancreatic Islets [J].

An, Wenjiao ;

Li, Yin ;

Xu, Geyang ;

Zhao, Jing ;

Xiang, Xinxin ;

Ding, Li ;

Li, Jing ;

Guan, Youfei ;

Wang, Xian ;

Tang, Chaosu ;

Li, Xiaoying ;

Mulholland, Michael ;

Zhang, Weizhen .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2010, 26 (4-5) :707-716

[2] Ghrelin-producing epsilon cells in the developing and adult human pancreas [J].

Andralojc, K. M. ;

Mercalli, A. ;

Nowak, K. W. ;

Albarello, L. ;

Calcagno, R. ;

Luzi, L. ;

Bonifacio, E. ;

Doglioni, C. ;

Piemonti, L. .

DIABETOLOGIA, 2009, 52 (03) :486-493

[3] Glucose and Weight Control in Mice with a Designed Ghrelin O-Acyltransferase Inhibitor [J].

Barnett, Brad P. ;

Hwang, Yousang ;

Taylor, Martin S. ;

Kirchner, Henriette ;

Pfluger, Paul T. ;

Bernard, Vincent ;

Lin, Yu-yi ;

Bowers, Erin M. ;

Mukherjee, Chandrani ;

Song, Woo-Jin ;

Longo, Patti A. ;

Leahy, Daniel J. ;

Hussain, Mehboob A. ;

Tschoep, Matthias H. ;

Boeke, Jef D. ;

Cole, Philip A. .

SCIENCE, 2010, 330 (6011) :1689-1692

[4] The endocrine response to ghrelin as a function of gender in humans in young and elderly subjects [J].

Broglio, F ;

Benso, A ;

Castiglioni, C ;

Gottero, C ;

Prodam, F ;

Destefanis, S ;

Gauna, C ;

van der Lely, AJ ;

Deghenghi, R ;

Bo, M ;

Arvat, E ;

Ghigo, E .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (04) :1537-1542

[5] Ghrelin Directly Stimulates Glucagon Secretion from Pancreatic α-Cells [J].

Chuang, Jen-Chieh ;

Sakata, Ichiro ;

Kohno, Daisuke ;

Perello, Mario ;

Osborne-Lawrence, Sherri ;

Repa, Joyce J. ;

Zigman, Jeffrey M. .

MOLECULAR ENDOCRINOLOGY, 2011, 25 (09) :1600-1611

[6] A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans [J].

Cummings, DE ;

Purnell, JQ ;

Frayo, RS ;

Schmidova, K ;

Wisse, BE ;

Weigle, DS .

DIABETES, 2001, 50 (08) :1714-1719

[7] Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion [J].

Date, Y ;

Nakazato, M ;

Hashiguchi, S ;

Dezaki, K ;

Mondal, MS ;

Hosoda, H ;

Kojima, M ;

Kangawa, K ;

Arima, T ;

Matsuo, H ;

Yada, T ;

Matsukura, S .

DIABETES, 2002, 51 (01) :124-129

[8] Type VIII adenylyl cyclase in rat beta cells: coincidence signal detector/generator for glucose and GLP-1 [J].

Delmeire, D ;

Flamez, D ;

Hinke, SA ;

Cali, JJ ;

Pipeleers, D ;

Schuit, F .

DIABETOLOGIA, 2003, 46 (10) :1383-1393

[9] The contractile effect of the ghrelin receptor antagonist, D-Lys3-Ghrp-6, in rat fundic strips is mediated through 5-HT receptors [J].

Depoortere, I ;

Thijs, T ;

Peeters, T .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2006, 537 (1-3) :160-165

[10] Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in β-cells -: Implication in the glycemic control in rodents [J].

Dezaki, K ;

Hosoda, H ;

Kakei, M ;

Hashiguchi, S ;

Watanabe, M ;

Kangawa, K ;

Yada, T .

DIABETES, 2004, 53 (12) :3142-3151

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