Johannes D. Veldhuis, MD


March 15, 2000

In This Article

Glucagon-like Peptides in Aging

Glucagon-like peptide-1 (GLP-1), the main product of the posttranslational processing of proglucagon in the small intestine, is produced in response to a mixed meal. This peptide, along with GIP (gastric inhibitory peptide), may mediate much of the so-called 'incretin effect' (augmented postprandial insulin secretion following oral compared with intravenous glucose administration due to the effect of intestinal hormones). In the baboon, a specific GLP-1 antagonist blocks the incretin effect, and GLP-1 knockout mice show glucose intolerance. At the pancreatic beta cell, GLP-1 is a potent insulin secretagogue, defining GLP-1 as a new incretin.

Intravenous infusion of GLP-1 in healthy humans is a powerful insulin secretagogue that acts by potentiating the insulinotropic action of glucose. GLP-1 may exert other actions on the stomach and brain, such as delaying gastric emptying and inducing satiety, respectively. The slower gastric emptying delays nutrient entry to the intestine and thereby diminishes meal-induced glucose excursions. The pathophysiologic roles of reduced GLP-1 action, if any, in aging-associated glucose intolerance are not yet known. Although GLP-1 deficiency does not occur in type 2 diabetes, possible future therapeutic applications for GLP-1 may be to heighten insulin secretion, augment glucose disposal, and repress postprandial glucagon production.[22]