BINDING-SPECIFICITY AND SIGNAL-TRANSDUCTION OF RECEPTORS FOR GLUCAGON-LIKE PEPTIDE-1(7-36)AMIDE AND GASTRIC-INHIBITORY POLYPEPTIDE ON RINM5F INSULINOMA CELLS

Glucagon-like peptide-1(7-36)amide (GLP-1(7-36) amide) and gastric inh ibitory polypeptide (GIP), peptides of the glucagon family, stimulate insulin secretion in vitro and in vivo. They possess high N-terminal s equence homology. Binding studies with I-125-labelled GIP and I-125-la belled GLP-1(7-36)amide were performed in RINm5F insulinoma cells to i nvestigate receptor specificity and to compare both receptors directly . Both binding sites were highly ligand-specific: GIP did not bind to the GLP-1(7-36)amide receptor and vice versa. Both peptides increased intracellular cyclic AMP levels; GLP-1(7-36)amide was 100-fold more po tent in stimulating cyclic AMP production when compared with GIP. At r anges of 1-10 nmol GLP-1(7-36)amide/l and 0.1-10 nmol GIP/l, correspon ding to submaximal binding concentrations, the hormones showed an addi tive effect on cyclic AMP production. The N-terminal portion of GIP wa s important for binding, as GIP(1-30) showed almost full binding and b iological activity. GIP(17-42) bound in a concentration-dependent mann er with approximately 500-fold lower potency than GIP. At concentratio ns of up to 10 mumol GIP(17-42)/l no stimulation of cyclic AMP was obs erved.