EFFECT OF GLP 1 ON GLUCOSE UPTAKE & HEPATIC GLUCOSE OUTPUT IN OBESITY

GLP-1是一种由肠道分泌的促胰岛素激素，可增加胰岛素分泌以应对食物，降低2型糖尿病患者的血糖。在体外实验的基础上，我们提出GLP-1除了具有胰岛素性外，还可能具有胰岛素仿性，即它也可能具有与胰岛素相似的内在葡萄糖处理特性。我们正在研究超重的个体，因为他们的肥胖已经导致胰岛素介导的葡萄糖排入组织的减少。我们认为，如果葡萄糖处理已经正常，那么我们可能不会在GLP-1存在和不存在的情况下看到葡萄糖处理的差异。事实上，在正常体重的年轻男性中，我们并没有看到差异（JCEM 2399-2404, 1999）。我们正在使用葡萄糖钳技术在血糖正常的条件下进行本研究。这包括两个单独的学习日。第一项研究在0-60分钟内连续注入GLP-1 （1.5 pmol/kg min）。60分钟时终止GLP-1输注，血糖维持60-120分钟。从-120到+120分钟注入氚化葡萄糖，以评估肝脏对葡萄糖动力学的贡献。在GLP-1研究后，测量每个人的血浆胰岛素水平，并进行第二项研究，在0-60分钟内注入胰岛素代替GLP-1，以模仿个体对GLP-1的胰岛素反应。然后计算每个人在每个研究日的葡萄糖消失（处置）率。在第一次和第二次研究中处理的任何差异都可以归因于GLP-1。

GLP-1 is an insulinotropic hormone secreted by the intestine that augments insulin secretion in response to food and lowers blood glucose in type 2 diabetics. As well as being insulinotropic, we proposed, based on in vitro work, that GLP-1 might also be insulinomimetic, i.e., it might also have some intrinsic glucose disposal properties similar to insulin. We are studying overweight individuals as they already have a reduction in insulin-mediated glucose disposal into tissues due to their obesity. We argued that if glucose disposal were already normal, then we might not see a difference in glucose disposal in the presence and absence of GLP-1. In normal-weight young men, indeed, we did not see a difference (JCEM 2399-2404, 1999). We are conducting the present study under conditions of euglycemia using glucose clamp technology. This involves two separate study days. The first study is performed with a primed continuous infusion of GLP-1 (1.5 pmol/kg min) from 0-60 minutes. At 60 minutes the GLP-1 infusion is terminated and euglycemia maintained from 60-120 minutes. Tritiated glucose is infused from -120 to +120 minutes in order to evaluate the contribution of the liver to glucose kinetics. After the GLP-1 study, each individual's plasma insulin levels are measured and a second study is done whereby insulin is infused in place of GLP-1 from 0-60 minutes to mimic the individual's insulin response to GLP-1 from the first study. The rate of disappearance (disposal) of glucose is then calculated for each individual under each study day. Any difference in disposal between the first and second study can then be attributed to GLP-1.