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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 摘要 以前2型糖尿病（T2 DM）被认为是一种成人疾病;然而，儿童T2 DM的发病率正在上升。因此，并发症可能发生在较早的年龄，强调了改善儿童人群血糖控制的重要性。餐后高血糖显著导致T2 DM患者血糖控制不良。我们现在知道，除了胰岛素，其他激素（胰高血糖素，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重要因素。胰腺激素胰淀素和肠促胰岛素GLP-1的减少已成为T2 DM胃排空和餐后高血糖改变的促成因素。尽管对成人T2 DM患者餐后高血糖相关异常了解较多，但儿科人群的相关信息很少。该方案将检查摄入混合餐后健康瘦型肥胖儿童（有和无糖尿病）的胃排空、胰高血糖素、GLP-1和胰淀素分泌。受试者的年龄和坦纳分期匹配。本项目的目的是通过比较我们的研究组与肥胖（正常葡萄糖耐量）和健康（瘦）对照组，更好地了解T2 DM患者餐后葡萄糖稳态的代谢适应。PI的长期目标是使用本方案收集的数据制定K-23提案，通过在T2 DM儿童中使用胰淀素和GLP-1类似物改善餐后高血糖症，纳入新的治疗选择。 I. 假设 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，胃排空加速 二.具体目标 采用混合餐挑战研究肥胖和T2 DM青少年的餐后代谢。具体而言，我们将测量以下餐后代谢参数： 1.餐后血糖波动 2.胃排空 3.胰岛素、胰淀素、胰高血糖素和GLP-1分泌 4. Ghrelin分泌 5.葡萄糖转换率

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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