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Exogenous and endogenous ghrelin counteracts GLP‐1 action to stimulate cAMP signaling and insulin secretion in islet β‐cells
Author(s) -
Damdindorj Boldbaatar,
Dezaki Katsuya,
Kurashina Tomoyuki,
Sone Hideyuki,
Rita Rauza,
Kakei Masafumi,
Yada Toshihiko
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.06.034
Subject(s) - ghrelin , medicine , endocrinology , forskolin , islet , insulin , endogeny , activator (genetics) , chemistry , pancreatic islets , receptor , downregulation and upregulation , biology , biochemistry , gene
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 [Ca 2+ ] i increases in single β‐cells, and these potentiations were attenuated by ghrelin. Ghrelin suppressed [Ca 2+ ] 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, [Ca 2+ ] i and insulin release in islet β‐cells, positioning ghrelin as a modulator of insulinotropic GLP‐1.