Larsson H, Holst J J, Ahrén B
Department of Medicine, Lund University, Malmö, Sweden.
Acta Physiol Scand. 1997 Aug;160(4):413-22. doi: 10.1046/j.1365-201X.1997.00161.x.
The effect of glucagon-like peptide-1 (GLP-1) on hepatic glucose production and peripheral glucose utilization was investigated with or without infusion of somatostatin to inhibit insulin and glucagon secretion in 13 healthy, non-diabetic women aged 59 years. After 120 min 3-(3)H-glucose infusion, GLP-1 was added (4.5 pmol kg(-1) bolus + 1.5 pmol kg(-1) min(-1)). Without somatostatin (n = 6), GLP-1 decreased plasma glucose (from 4.8 +/- 0.2 to 4.2 +/- 0.3 mmol L(-1), P = 0.007). Insulin levels were increased (48 +/- 3 vs. 243 +/- 67 pmol L(-1), P = 0.032), as was the insulin to glucagon ratio (P = 0.044). The rate of glucose appearance (Ra) was decreased (P = 0.003) and the metabolic clearance rate of glucose (MCR) was increased during the GLP-1 infusion (P = 0.024 vs. saline). Also, the rate of glucose disappearance (Rd) was reduced during the GLP-1 infusion (P = 0.004). Since Ra was reduced more than Rd, the net glucose flow was negative, which reduced plasma glucose. Somatostatin infusion (500 microg h(-1), n = 7) abolished the effects of GLP-1 on plasma glucose, serum insulin, insulin to glucagon ratio, Ra, Rd, MCR and net glucose flow. The results suggest that GLP-1 reduces plasma glucose levels mainly by reducing hepatic glucose production and increasing the metabolic clearance rate of glucose through indirectly increasing the insulin to glucagon ratio in healthy subjects.
在13名年龄为59岁的健康非糖尿病女性中，研究了胰高血糖素样肽-1（GLP-1）对肝糖生成和外周葡萄糖利用的影响，实验分为输注生长抑素抑制胰岛素和胰高血糖素分泌与不输注生长抑素两组。在输注3-(3)H-葡萄糖120分钟后，添加GLP-1（4.5 pmol kg(-1)推注 + 1.5 pmol kg(-1) min(-1)）。不输注生长抑素组（n = 6），GLP-1使血浆葡萄糖降低（从4.8 +/- 0.2降至4.2 +/- 0.3 mmol L(-1)，P = 0.007）。胰岛素水平升高（48 +/- 3对243 +/- 67 pmol L(-1)，P = 0.032），胰岛素与胰高血糖素比值也升高（P = 0.044）。葡萄糖出现率（Ra）降低（P = 0.003），在输注GLP-1期间葡萄糖代谢清除率（MCR）升高（与输注生理盐水相比，P = 0.024）。此外，在输注GLP-1期间葡萄糖消失率（Rd）降低（P = 0.004）。由于Ra降低幅度大于Rd，葡萄糖净流量为负，从而降低了血浆葡萄糖。输注生长抑素（500 microg h(-1)，n = 7）消除了GLP-1对血浆葡萄糖、血清胰岛素、胰岛素与胰高血糖素比值、Ra、Rd、MCR和葡萄糖净流量的影响。结果表明，在健康受试者中，GLP-1主要通过降低肝糖生成并间接增加胰岛素与胰高血糖素比值来提高葡萄糖代谢清除率，从而降低血浆葡萄糖水平。
