Abstract
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 β-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-lys3]-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 β-cells, positioning ghrelin as a modulator of insulinotropic GLP-1.
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