Effects of efaroxan on insulin release from pancreatic βcells / 中国药理学通报

ABSTRACT

Aim To study the insulinotropic effects of Efaroxan and the underlying mechanism in rat βcells. Methods Pancreatic islets were isolated by college-nase p digestion.Radioimmunoassay was used to meas-ure insulin secretion and cAMP level in rat pancreatic islets.Results Efaroxan only potentiated insulin se-cretion at high glucose concentrations(8.3,1 1 .1 mmol ·L -1 )but not at low glucose concentrations.KU1 4R,an antagonist of Efaroxan,remarkably inhibited Efarox-an-potentiated insulin secretion;and similarly,KU1 4R significantly inhibited forskolin-induced and IBMX-in-duced insulin secretion.cAMP measurement showed that forskolin and IBMX significantly increased cAMP levels,but Efaroxan and KU1 4R had no effects on cAMP content in pancreatic islets.Conclusion The mechanism of Efaroxan-potentiated insulin secretion is related to downstream of cAMP signaling pathway, KU1 4R antagonized the downstream of cAMP signaling leading to its inhibitory effects on Efaroxan,forskolin and IBMX-induced insulin secretion.