Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes
Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes
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DOI：
10.2337/diabetes.49.4.611
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发表时间：
2000-04-01
期刊：
影响因子：
7.7
通讯作者：
Rizza, RA
中科院分区：
文献类型：
--
作者：
Vella, A;Shah, P;Rizza, RA
虽然已经确定胰高血糖素样肽1（7-36）酰胺（GLP-1）是胰岛素分泌的有效刺激物，但其对胰岛素作用和葡萄糖有效性的影响尚不清楚。为了确定GLP-1是否会增加胰岛素的作用和葡萄糖的有效性，我们对2型糖尿病患者进行了两次研究。两种情况下都在夜间注射胰岛素，以确保基线葡萄糖浓度具有可比性。在学习的早晨，GLP-1 (1.2 pmol。公斤(1)。Min（-1）或生理盐水与生长抑素和替代量的胰高血糖素一起输注。葡萄糖也以一种模仿碳水化合物餐后观察到的模式注入。胰岛素浓度要么保持在基础水平不变（n = 6），要么改变以形成膳食胰岛素谱（n = 6）。在基础胰岛素输注（1.21 +/- 0.15 vs. 1.32 +/- 0.10 mol/l / 6 h）和膳食胰岛素输注（0.56 +/- 0.14 vs. 0.56 +/- 0.10 mol/l / 6 h）期间，GLP-1和生理盐水研究期间葡萄糖浓度的增加几乎相同。在基础和餐后胰岛素输注期间，葡萄糖消失在葡萄糖输注开始后迅速增加，其速率在GLP-1和生理盐水研究日没有差异。在基础胰岛素（-2.7 +/- 0.3 vs. 3.1 +/- 0.2 mu mol/kg）和膳食胰岛素（3.1 +/- 0.4 vs. 3.0 +/- 0.6 mu mol/kg）输注期间，GLP-1和生理盐水研究日对内源性葡萄糖产生的抑制也具有可比性。我的结论是，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有效性的影响可以忽略不计。这些数据有力地支持了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不是通过改变胰腺外糖代谢来改善2型糖尿病患者血糖控制的概念。
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 . kg(-1) . 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 +/- 0.10 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 mu mol/kg) and prandial(3.1 +/- 0.4 vs. 3.0 +/- 0.6 mu mol/kg) insulin infusions. me 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.