Dose-related effects of GLP-1 on insulin secretion, insulin sensitivity, and glucose effectiveness in mice

GLP-1 on insulin secretion, insulin sensitivity, and glucose effectiveness in mice. Am. J. Physiol. 277 (Endocrinol. Metab. 40): E996–E1004, 1999.—We examined the dose-related net effects of glucagon-like peptide 1 (GLP-1) on insulin secretion, insulin sensitivity, and glucose disposal as derived from the minimal model of glucose disappearance in anesthetized mice. GLP-1 dose dependently potentiated insulin secretion after glucose administration, with the half-maximal effect at 1 nmol/kg. GLP-1 also dose dependently reduced the area under the glucose curve (AUCglucose) and increased the glucose elimination rate (KG) but did not affect the glucose effective-ness (SG). Furthermore, the insulin sensitivity index (SI) was reduced after administration of GLP-1. Because insulin secre-tion was stimulated to a larger degree than SI was reduced, the peptide increased the global disposition index (GDI 5 AUCinsulin 3 SI). Matching plasma insulin levels after GLP-1 by exogenous insulin reproduced the influences of GLP-1 on AUCglucose, KG, SI, and GDI. Finally, the GLP-1 receptor antagonist exendin-3-(9—39) inhibited the actions of GLP-1. We conclude that GLP-1 increases glucose tolerance in the mouse mainly by potently stimulating insulin secretion. glucagon-like peptide 1; glucose disposal; mouse GLUCAGON-LIKE PEPTIDE 1 [GLP-1-(7—36) amide (GLP-1)] is a gut hormone that is released from the intestinal L cells during a meal and that, as an incretin factor