Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C

In man, glucagon-like peptide-I-(7-37) [GLP-I-(7-37)] is the most potent endogenous insulin-stimulating hormone. Although GLP-I-(7-37)-stimulated insulin secretion from the beta-cell is associated with an increase in cAMP accumulation, little is known about the signal transduction pathways used by this peptide. Using a cDNA encoding a high affinity rat GLP-I-(7-37) receptor [Kd = 4.1 nM for GLP-I-(7-37); Kd = 1 microM for GLP-I-(1-36) amide] expressed in a monkey kidney cell line (COS-7), we have demonstrated that the receptor is not only coupled to adenylyl cyclase, but is associated with an increase in the free cytosolic calcium level ([Ca2+]i). GLP-I-(7-37) increased both cAMP and [Ca2+]i in a dose-dependent manner and with equal potency (ED50 = 2.0 nM). The major source of the increased [Ca2+]i was found to be through the release of intracellular pools of Ca2+ associated with an increase in phosphoinositol turnover. Northern blot hybridization studies demonstrated that the GLP-I-(7-37) receptor gene w...