The effects of GLP-1 on insulin release in young and old rats in the fasting state and during an intravenous glucose tolerance test.

Glucose intolerance is a common feature of the aging process, and aging per se is an etiologic factor for Type II diabetes mellitus. To characterize the beta cell abnormalities that occur with aging, we looked at the serum glucose and insulin levels of six young (3-month) and six old (22-month) Wistar rats at 0, 2, 4, 7, 10, 15, 20, and 30 minutes after an intravenous glucose load (IVGTT, 0.5 g/kg glucose). We found that the fasting glucose and insulin levels were not significantly different between young and old rats. However, peak glucose levels were significantly higher in the old (349 +/- 10 mg/dl) compared to the young (250 +/- 7 mg/dl) animals (p < .0001). Insulin levels in the young animals peaked at 2 minutes (859 +/- 171 pmol/l) with a quick return toward fasting levels by 7 minutes. The old animals had a delayed and blunted insulin response to glucose, achieving lower peak insulin levels (656 +/- 164 pmol/l) 7 minutes after the glucose load. As insulin levels are also positively modulated by incretin hormones, we quantitated the fasting insulin responses of young and old animals to .05, 0.1, 0.2, 0.4, and 0.5 nmol/kg intravenous glucagon-like peptide-1 (GLP-1), the most potent incretin known. Insulin responses were similar in both age groups, with maximum insulin responses seen at 0.4 nmol/kg. GLP-1, in conjunction with the IVGTT, restored the acute insulin response to glucose and increased the clearance of glucose in the old animals. It therefore appears that old animals have an impaired glucose-mediated insulin release but maintain their insulin responsivity to GLP-1. This makes it a likely candidate in the treatment of Type II diabetes.