THE EFFECT OF THE GLUCAGON SUPPRESSORS PRAMLINTIDE AND EXENATIDE ON POSTPRANDIAL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 胰高血糖素抑制剂的使用？？普兰林肽和艾塞那肽在成人T2 DM患者中已得到充分证实，但缺乏关于在儿童T2 DM中有效降糖作用的信息。我们实验室先前的研究表明，T2 DM儿童中存在未减轻的早期餐后高胰高血糖素血症，导致显著的餐后高血糖。需要胰岛素治疗的T2 DM儿童存在胰岛素、胰淀素和GLP-1缺乏。胰淀素和GLP-1都是有效的内源性胰高血糖素抑制剂。将在需要胰岛素的T2 DM儿童中检测胰淀素类似物普兰林肽和GLP-1受体激动剂依塞那肽的降糖和降胰高血糖素作用。将使用最低成人推荐剂量。随着儿童人群中T2 DM发病率的增加，我们有责任研究新的治疗方法，以改善血糖控制并预防与糖尿病相关的长期微血管和大血管并发症。 我们假设餐前给予胰高血糖素抑制剂将降低接受胰岛素治疗的T2 DM儿童的餐后高血糖症和高胰高血糖素血症。目的是确定胰高血糖素抑制剂普兰林肽和艾塞那肽独立给药对以下方面的影响： a）葡萄糖波动 B）胰高血糖素浓度。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The use of glucagon suppressors¿?? pramlintide and exenatide is well established in adult patients with T2DM, but there is a lack of information regarding an effective glucose lowering effect in pediatric T2DM. Previous studies from our laboratory showed that there is unabated early postprandial hyperglucagonemia in children with T2DM contributing to the marked postprandial hyperglycemia. There is insulin, amylin and GLP-1 deficiency in children with T2DM requiring insulin therapy. Both amylin and GLP-1 are potent endogenous glucagon suppressors. The glucose and glucagon lowering effect of the amylin analog pramlintide and the GLP-1 receptor agonist exenatide will be tested in insulin requiring children with T2DM. The lowest adult recommended doses would be used. With an increasing incidence of T2DM in the pediatric population, it is incumbent upon us to research new therapies in an effort to improve glycemic control and prevent the long-term micro and macrovascular complications associated with diabetes. We hypothesize that preprandial administration of a glucagon suppressor will decrease postprandial hyperglycemia and hyperglucagonemia in insulin treated children with T2DM. The objective is to determine the effect of the glucagon suppressors pramlintide and exenatide independently administered on: a) Glucose excursions b) Glucagon concentrations.