GLUCAGON-LIKE PEPTIDE-I ANALOGS - EFFECTS ON INSULIN-SECRETION AND ADENOSINE-3',5'-MONOPHOSPHATE FORMATION

Glucagon-like peptide l-(7-37) [GLP-I-(7-37)] is a 31-amino acid hormone which may have an important role in the regulation of insulin secretion. It is processed from pre-proglucagon and found in the pancreas, brain, and, in highest quantity, intestine. In previous studies we found that GLP-I-(7-37) is a potent insulin secretagogue, and its effect was indistinguishable from that of GLP-I-(7-36) amide at concentrations of 10_n M. Herein we report insulinotropic effects of additional GLP-I analogs. GLP-I-(7-34) had no stimulatory effect on insulin release at 10-10M, but had a partial effect at 10-9M and was as active as GLP-I-(7-37) at 10-8M. GLP-I-(7-33) had no effect at any concentration tested. GLP-I-(8-37) caused no significant effect on insulin release at 10-9and 10-8M, but did have an effect at the high concentration of 10-7M. Similar results were found with cAMP formation in the βTC1 line. In this system GLP-I-(7-34) was less potent than GLP-I-(7-37) at a concentration of 5  10-9M. GLP-I-(7-33) had only about 0.1% the potency of GLP-I-(7-37); thus, there is good agreement between cAMP formation in the β-cell line and insulin secretion from the perfused pancreas experiments. We conclude that histidine in the 7 position in the N-terminus of GLP-I-(7-37) is crucial for cAMP formation and insulin secretion, and that removal of the last three C-terminus residues of GLP-I-(7-37) results in only partial loss of activity; the residue in the 34 position is, however, essential for the insulinotropic action. © 1990 by The Endocrine Society.