EFFECTS OF GLUCAGON ON CARBOHYDRATE METABOLISM IN TYPE 2 DIABETES MELLITUS

胰高血糖素对 2 型糖尿病碳水化合物代谢的影响

• 批准号: 6265007
• 负责人: ROBERT A. RIZZA
• 金额: $ 2.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265007
• 关键词: carbohydrate metabolism; clinical research; glucagon; hormone regulation /control mechanism; human subject; hyperglycemia; insulin; noninsulin dependent diabetes mellitus; somatostatin

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.

本研究的目的是确定2型糖尿病受试者在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症。 8例2型糖尿病受试者在两种情况下进行了研究。 在这两种情况下，志愿者接受了50克葡萄糖饮料，而他们的内源性激素的产生被生长抑素抑制。 输注胰岛素以模拟糖尿病餐后特征。 以1.25 ng/kg/min的速率输注胰高血糖素，从时间0开始以防止餐后胰高血糖素浓度下降，或从2小时开始以产生血浆胰高血糖素浓度的短暂下降。迄今为止进行的研究表明，当2型糖尿病患者的胰岛素分泌受损时，胰高血糖素的非抑制性对餐后高血糖没有显著影响。我们观察到口服葡萄糖后胰岛素浓度立即出现不可预见的下降。 这是由于从时间零点开始的“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不必要的胰岛素水平下降。 生长抑素将在时间-240开始。 将继续调整胰岛素输注，以在整个研究期间以相同的胰岛素输注速率维持过夜血糖。 对于这项修改，我们已经从IRB（1/12/99）和辐射安全部获得了四次（而不是批准的三次）研究志愿者的批准。我们预计无需超过批准的志愿者数量和每名志愿者完成4项研究。 我们计划继续研究志愿者，并在2000年底完成研究。