Ahrén B, Pacini G
Department of Medicine, Lund University, S-205 02 Malmö, Sweden.
Am J Physiol. 1999 Dec;277(6):E996-E1004. doi: 10.1152/ajpendo.1999.277.6.E996.
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 (AUC(glucose)) and increased the glucose elimination rate (K(G)) but did not affect the glucose effectiveness (S(G)). Furthermore, the insulin sensitivity index (S(I)) was reduced after administration of GLP-1. Because insulin secretion was stimulated to a larger degree than S(I) was reduced, the peptide increased the global disposition index (GDI = AUC(insulin) x S(I)). Matching plasma insulin levels after GLP-1 by exogenous insulin reproduced the influences of GLP-1 on AUC(glucose), K(G), S(I), 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.
我们通过麻醉小鼠体内葡萄糖消失的最小模型，研究了胰高血糖素样肽-1（GLP-1）对胰岛素分泌、胰岛素敏感性和葡萄糖处置的剂量相关净效应。给予葡萄糖后，GLP-1呈剂量依赖性增强胰岛素分泌，半数最大效应浓度为1 nmol/kg。GLP-1还呈剂量依赖性降低葡萄糖曲线下面积（AUC(葡萄糖)）并提高葡萄糖清除率（K(G)），但不影响葡萄糖效能（S(G)）。此外，给予GLP-1后胰岛素敏感性指数（S(I)）降低。由于胰岛素分泌受到的刺激程度大于S(I)降低的程度，该肽增加了整体处置指数（GDI = AUC(胰岛素)×S(I)）。通过外源性胰岛素使GLP-1给药后的血浆胰岛素水平匹配，重现了GLP-1对AUC(葡萄糖)、K(G)、S(I)和GDI的影响。最后，GLP-1受体拮抗剂艾塞那肽-3-(9-39)抑制了GLP-1的作用。我们得出结论，GLP-1主要通过强力刺激胰岛素分泌来提高小鼠的葡萄糖耐量。
