Beneficial effects of sub-chronic activation of glucagon-like peptide-1 (GLP-1) receptors on deterioration of glucose homeostasis and insulin secretion in aging mice.

Aging is associated with an increased incidence of glucose intolerance and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is an important insulinotropic peptide secreted from the gastrointestinal tract in response to nutrient absorption. The present study was designed to assess the sub-chronic glucose regulatory effects of the potent long-acting GLP-1 receptor agonist, (Val(8))GLP-1, in aging 45-49 week old mice. Daily injection of (Val(8))GLP-1 (25 n mol/kg body weight) for 12 days had no significant effect on food intake, body weight, non-fasting plasma glucose and insulin concentrations. However, after 12 days, the glycaemic response to intraperitoneal glucose was improved (P<0.05) in (Val(8))GLP-1 treated mice. In keeping with this, glucose-mediated insulin secretion was enhanced (P<0.05) and insulin sensitivity improved (P<0.05) compared to controls. These data indicate that sub-chronic activation of the GLP-1 receptor by daily treatment with (Val(8))GLP-1 counters aspects of the age-related impairment of pancreatic beta-cell function and insulin sensitivity.