Vella A, Shah P, Basu R, Basu A, Holst J J, Rizza R A
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Diabetes. 2000 Apr;49(4):611-7. doi: 10.2337/diabetes.49.4.611.
Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol x kg(-1) x min(-1)) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal (1.21 +/- 0.15 vs. 1.32 +/- 0.19 mol/l per 6 h) and prandial (0.56 +/- 0.14 vs. 0.56 +/- 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 +/- 0.3 vs. -3.1 +/- 0.2 micromol/kg) and prandial (-3.1 +/- 0.4 vs. -3.0 +/- 0.6 pmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.
尽管已有充分证据表明胰高血糖素样肽1（7-36）酰胺（GLP-1）是胰岛素分泌的强效刺激剂，但其对胰岛素作用和葡萄糖效能的影响尚不清楚。为了确定GLP-1是否能增强胰岛素作用和葡萄糖效能，对2型糖尿病患者进行了两次研究。两次研究均在夜间输注胰岛素，以确保基线血糖浓度具有可比性。在研究当天上午，输注GLP-1（1.2 pmol·kg⁻¹·min⁻¹）或生理盐水，同时输注生长抑素和补充量的胰高血糖素。葡萄糖也以模拟碳水化合物餐后通常观察到的模式进行输注。胰岛素浓度要么保持在基础水平不变（n = 6），要么变化以形成餐时胰岛素曲线（n = 6）。在基础胰岛素输注（每6小时1.21±0.15 vs. 1.32±0.19 mol/l）和餐时胰岛素输注（每6小时0.56±0.14 vs. 0.56±0.10 mol/l）期间，GLP-1研究日和生理盐水研究日的血糖浓度升高几乎相同。在基础胰岛素输注和餐时胰岛素输注期间，葡萄糖输注开始后，葡萄糖消失迅速增加至GLP-1研究日和生理盐水研究日无差异的速率。在基础胰岛素输注（-2.7±0.3 vs. -3.1±0.2 μmol/kg）和餐时胰岛素输注（-3.1±0.4 vs. -3.0±0.6 pmol/kg）期间，GLP-1研究日和生理盐水研究日对内源性葡萄糖生成的抑制作用也相当。我们得出结论，当胰岛素和胰高血糖素浓度匹配时，GLP-1对2型糖尿病患者的胰岛素作用或葡萄糖效能影响可忽略不计。这些数据有力地支持了以下观点，即GLP-1通过增加胰岛素分泌、抑制胰高血糖素分泌和延迟胃排空而非改变胰腺外葡萄糖代谢来改善2型糖尿病患者的血糖控制。
