Effect of C-terminal fragments of glucagon on insulin secretion in dogs

Although the insulinotropic action of glucagon is well known, which parts of the glucagon molecule play an importent role in its action remain to be elucidated. To investigate the direct effect of the C-terminal peptides of glucagon on the endocrine function of the pancreas, glucagon(17-29), (21-29), (23-29), and (25-29) were studied using an in situ local circulation system of the canine pancreas. These glucagon fragments, as well as glucagon(1-29), were infused into the superior pancreaticoduodenal artery (PA) in a dosage of 400 pmol for 10 minutes during 0.5% glucose or 0.5% arginine infusion, and plasma insulin (IRI) and glucagon (IRG) levels in the superior pancreaticoduodenal vein (PV) were determined. During the glucose infusion, plasma IRI increased significantly following the administration of glucagon(23-29), (21-29), (17-29), or (1-29), but not glucagon(25-29). In these experiments, plasma IRG increased significantly following infusion of glucagon(21-29), (17-29), or (1-29). During the arginine infusion, all of the glucagon fragments studied enhanced insulin secretion, whereas plasma IRG was increased following the administration of glucagon(21-29), (17-29), or (1-29). In these experiments with glucose or arginine infusion, blood glucose in the femoral artery (FA) did not change significantly except for glucagon(1-29), which increased the blood glucose level. In addition, the administration of graded doses of glucagon(21-29) [50, 150, and 400 pmol] during the glucose infusion elicited an increase in plasma IRI in a dose-related manner. From the present study, it is concluded that the C-terminal peptides of glucagon enhanced insulin release, and that glucagon(21-29) is the minimum structure among the C-terminal glucagon fragments to stimulate insulin secretion.