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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 使用胰高血糖素抑制剂？？普拉林肽和埃塞那肽在成年T2 DM患者中得到了很好的证实，但缺乏关于儿童T2 DM有效降糖效果的信息。我们实验室以前的研究表明，T2 DM儿童早期餐后高血糖并未减轻，这是导致显著餐后高血糖的原因之一。需要胰岛素治疗的T2 DM患儿存在胰岛素、胰淀素和GLP-1缺乏症。胰淀素和GLP-1都是内源性的胰高血糖素抑制因子。胰淀素类似物普拉林肽和GLP-1受体激动剂埃塞那肽的降糖和降糖作用将在需要胰岛素的T2 DM儿童中进行测试。将使用成人推荐的最低剂量。随着T2 DM在儿科人群中发病率的增加，我们有责任研究新的治疗方法，以努力改善血糖控制，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，在接受胰岛素治疗的T2 DM儿童中，餐前应用胰升糖素抑制剂可以降低餐后高血糖和高血糖。目的是确定单独应用胰升糖素抑制剂普拉林肽和埃塞那肽对以下各项的影响： A)葡萄糖漂移 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.