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

摘要

WestudiedinteractiveeffectsofinsulinotropicGLP‐1andinsulinostaticghrelinonratpancreaticislets.GLP‐1potentiatedglucose‐inducedinsulinreleaseandcAMPproductioninisolatedisletsand[Ca2+]iincreasesinsingleβ‐cells,andthesepotentiationswereattenuatedbyghrelin.Ghrelinsuppressed[Ca2+]iresponsestoanadenylatecyclaseactivatorforskolin.Moreover,GLP‐1‐inducedinsulinreleaseandcAMPproductionweremarkedlyenhancedby[d‐lys3]‐GHRP‐6,aghrelinreceptorantagonist,inisolatedislets.Theseresultsindicatethatbothexogenousandendogenousislet‐derivedghrelincounteractsglucose‐dependentGLP‐1actiontoincreasecAMPproduction,[Ca2+]iandinsulinreleaseinisletβ‐cells,positioningghrelinasamodulatorofinsulinotropicGLP‐1...