THE ROLE OF AMYLIN AND INCRETINS ON POSTPRANDIAL METABOLISMS IN ADOLESCENTS W

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。 摘要 过去，2型糖尿病(T2 DM)被认为是成人的疾病；然而，儿童T2 DM的发病率呈上升趋势。因此，并发症可能发生在较早的年龄，强调了改善儿科人群血糖控制的重要性。餐后高血糖是2型糖尿病患者血糖控制不良的重要原因。我们现在了解到，除了胰岛素之外，其他激素(胰升糖素、胰淀素和GLP-1)可能在餐后葡萄糖代谢中发挥作用。胃排空的作用越来越被认为是调节葡萄糖进入循环的一个重要因素。胰淀素和胰岛素GLP-1的异常是T2 DM胃排空改变和餐后高血糖的重要因素。尽管人们对成人T2 DM患者的餐后高血糖异常了解很多，但在儿科人群中可获得的信息却很少。该方案将检测健康的肥胖儿童在摄入混合膳食后的胃排空、胰高血糖素、GLP-1和胰淀素分泌。主题将是年龄和晒黑阶段相匹配的。该项目的目标是通过将我们的研究组与肥胖(糖耐量正常)和健康(瘦)对照组进行比较，更好地了解T2 DM患者餐后血糖稳态的代谢适应。PI的长期目标是利用该方案收集的数据制定一项K-23方案，通过在T2 DM儿童中使用胰淀素和GLP-1类似物来改善餐后高血糖，纳入新的治疗方案。 一、假说 与健康(瘦)和肥胖对照组相比，T2 DM青少年餐后胰淀素和GLP-1分泌减少，胃排空加快 二、具体目标 研究肥胖和2型糖尿病青少年的餐后代谢。具体地说，我们将测量以下餐后代谢参数： 1.餐后血糖漂移 2.胃排空 3.胰岛素、胰淀素、胰高血糖素和GLP-1分泌 4.胃促生长素分泌 5.葡萄糖周转率

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. ABSTRACT Previously type 2 diabetes mellitus (T2DM) was considered a disease of the adult; however, the incidence of T2DM in children is on the rise. Consequently, complications may occur at an earlier age, underscoring the importance of improving glycemic control in the pediatric population. Postprandial hyperglycemia contributes significantly to poor glycemic control in T2DM. We now understand that in addition to insulin other hormones (glucagon, amylin and GLP-1) may play a role in the postprandial glucose metabolism. The role of gastric emptying has been increasingly recognized as an important factor in regulating glucose appearance into the circulation. Abnormalities in the pancreatic hormone amylin and the incretin GLP-1 have emerged as contributors to the alterations in gastric emptying and postprandial hyperglycemia in T2DM. Although much is know about the abnormalities related to postprandial hyperglycemia in adults with T2DM, little information is available in the pediatric population. This protocol will examine gastric emptying, glucagon, GLP-1 and amylin secretions in healthy lean, obese children with and without diabetes post-ingestion of a mixed meal. The subject will be age and Tanner stage matched. The goal of this project is to better understand the metabolic adaptations of postprandial glucose homeostasis in T2DM by comparing our study group to obese (normal glucose tolerance) and healthy (lean) controls. The long-term goal for the PI is to use the data gathered with this protocol to develop a K-23 proposal incorporating new therapeutic options through the use of amylin and GLP-1 analogs in children with T2DM to improve postprandial hyperglycemia. I. HYPOTHESIS Adolescents with T2DM will have decreased postprandial amylin and GLP-1 secretion and accelerated gastric emptying when compared with healthy (lean) and obese controls II. SPECIFIC AIMS To study postprandial metabolism in obese and T2DM adolescents using a mixed meal challenge. Specifically we will be measuring the following parameters of postprandial metabolism: 1. Postprandial glucose excursions 2. Gastric emptying 3. Insulin, amylin, glucagon and GLP-1 secretion 4. Ghrelin secretion 5. Glucose Turnover rate