GLP-1 DEPOLARIZES THE RAT PANCREATIC BETA-CELL IN A NA-DEPENDENT MANNER()

An intestinal hormone glucagon-like-peptide-1 (GLP-1) is a prominent c andidate for incretin. In vitro experiment showed (Fridolf and Ahren, Mol. Cell. Endocrinol., 96 (1993) 85-90) that GLP-1 increased both ins ulin secretion and the efflux of Ca-45(2+) in a Na+-dependent manner. Further, GLP-1 depolarizes the pancreatic beta cells in the presence o f high concentration of glucose. Here, we report the effect of GLP-1 o n the membrane potential with a physiological concentration of glucose in perforated patch clamp of primary cultured rat beta cells. 10 nM G LP-1 depolarized the beta cell, which was completely reversed by repla cing Na+ with the impermeant molecule N-methyl-D-glucamine (NMDG). The Ca2+ channel blocker, Co2+ suppressed the Ca2+ spikes without hyperpo larizing the cell. GLP-1-induced insulin secretion in perifused islets was also suppressed by a prior replacement of Na+ with NMDG. In addit ion, GLP-1 slightly augmented the long-lasting Ba2+ current, which was reverted to the control level by a selective inhibitor of protein kin ase A, H-89. These results indicate: (i) GLP-1 depolarizes the beta ce ll by activating the membrane Na+ permeability; (ii) GLP-1 slightly mo dulates the L-type Ca2+ channel probably through protein kinase A; and (iii) at least in part, these mechanisms may be involved in the insul in secretion induced by GLP-1.