26RFa, a novel orexigenic neuropeptide, inhibits insulin secretion in the rat pancreas

26RFa is a novel orexigenic neuropeptide identified as the endogenous ligand of the orphan G protein-coupled receptor GPR103. GPR103 shares sequence identity with the receptors for neuropeptide-Y and Galanin, two peptides known to inhibit Insulin secretion. We have investigated the effect of 26RFa on Insulin and glucagon secretion in the perfused rat pancreas. 26RFa dose-dependently reduced glucose-induced Insulin release, inhibited the Insulin responses to both arginine and exendin-4 and did not affect glucagon output. The inhibitory effect of 26RFa on exendin-4-induced Insulin secretion was not observed in pancreata from pertussis toxin-treated rats, thus suggesting that 26RFa may inhibit Insulin secretion, at least in part, via a pertussis toxin-sensitive G(i) protein coupled to the adenylyl cyclase system.