EFFECTS OF GLUCAGON ON CARBOHYDRATE METABOLISM IN TYPE 2 DIABETES MELLITUS

本研究的目的是确定在2型糖尿病患者胰岛素分泌受损的情况下，胰高血糖素抑制缺乏是否会导致餐后高血糖。对8名2型糖尿病患者进行了两次研究。在两种情况下，志愿者都喝了50克葡萄糖饮料，同时他们的内源性激素分泌被生长抑素抑制。注射胰岛素来模拟糖尿病患者餐后的情况。以1.25 ng/kg/min的速率输注胰高血糖素，可以在零时间开始，以防止餐后胰高血糖素浓度下降，也可以在两小时开始，以使血浆胰高血糖素浓度短暂下降。目前已有研究表明，2型糖尿病患者在胰岛素分泌受损时，胰高血糖素的非抑制性对餐后高血糖的影响并不显著。我们观察到胰岛素浓度在口服葡萄糖摄入后立即意外下降。这是由于从零开始进行“标准基础胰岛素输注”和生长抑素。我们建议通过修改实验来避免这种情况。通过确定个体的“基础”胰岛素需求，可以避免胰岛素水平的不必要下降。生长抑素将在-240时间开始使用。胰岛素输注将继续调整以维持隔夜血糖，在相同的胰岛素输注速率下将持续整个研究。对于这次修改，我们已经获得了IRB（1999年1月12日）和辐射安全部门的批准，对志愿者进行了四次（而不是批准的三次）的研究。我们预计不需要超过批准的志愿者数量和每位志愿者完成四项研究。我们计划继续研究志愿者，并在2000年底完成这项研究。

The purpose of this study is to determine if lack of glucagon suppression causes postprandial hyperglycemia in the presence of impaired insulin secretion in subjects with type 2 diabetes mellitus. Eight subjects with type 2 diabetes mellitus have been studied on two occasions. On both occasions volunteers received a 50g glucose drink while their endogenous hormone production was inhibited by somatostatin. Insulin was infused to mimic a diabetic postprandial profile. Glucagon was infused at a rate of 1.25 ng/kg/min beginning either at time zero to prevent a fall in postprandial glucagon concentrations or beginning at two hours so as to create a transient fall in plasma glucagon concentrations. Studies conducted up till now indicate that the non-suppressibility of glucagon does not contribute significantly to high blood glucose after meal when insulin secretion is impaired in people with type 2 diabetes mellitus. We observed an unforeseen fall in the insulin concentrations immediately after oral glucose ingestion. This was due to a "standard basal insulin infusion" with somatostatin starting at time zero. We propose to avoid this by modifying the experiment. The unwanted fall of insulin levels can be avoided by determining individual "basal" insulin requirements. Somatostatin will be started at time -240. Insulin infusion will continue to be adjusted to maintain overnight euglycemia in the same insulin infusion rate will continue throught the study. For this modification, we have taken approval from IRB (1/12/99) and Radiation Safety to study volunteers four (rather than the approved three) times. We do not anticipate a need to go beyond the approved number of volunteers and the four studies per volunteer to finish the study. We plan to continue studying the volunteers and finish the study by the end of 2000.