ISLET FUNCTION & CLINICAL ANALYSES OF TRANSPLANT RECIPIENTS

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。 该项目的总体目标是研究随着时间的推移，胰岛细胞移植受者的葡萄糖耐量、胰岛素分泌和胰岛素作用的变化。通过确定这些受试者的胰岛素分泌和胰岛素作用之间的关系，我们希望确定目前的胰岛细胞移植方案是否能产生足以满足普遍存在的胰岛素抵抗程度的功能性β细胞团。将定义这些参数变化的自然历史。这些结果将作为判断优化胰岛细胞移植方案有效性的努力的基础。 将进行具体的实验，以确定随着时间的推移在以下方面的变化： 1.口服葡萄糖耐量和胰岛素对口服葡萄糖的分泌反应。 2.混合餐摄入后的胰岛素分泌反应和胰岛素原浓度。 3.使用最小模型测量静脉推注葡萄糖后的胰岛素分泌和胰岛素作用。胰岛素分泌反应相对于胰岛素敏感性指数的充分性将被评估。稳定的同位素将被用来确定葡萄糖周转的变化。 外源性葡萄糖输注引起血糖浓度升高和降低的葡萄糖-胰岛素分泌剂量-反应关系。

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 overall goal of this project is to study changes in glucose tolerance, insulin secretion and insulin action in islet cell transplant recipients over time. By defining the relationship between insulin secretion and insulin action in these subjects we hope to determien if current protocols for islet cell transplantation result in a level of functional beta cell masss that is adequate for the prevailing degree of insulin resistance. The natural history of changes in these parameters will be defined. These results will serve as a basis on which to judge efforts to optimize the efficacy of protocols for islet cell transplantation. Specific experiments will e conducted to define the changes over time in: 1. Oral glucose tolerance and insulin secretory responses to oral glucose. 2. Insulin secretory responses and proinsulin concentrations following mixed meal ingestion. 3. Measurements of insulin secretion and insulin action following administration of an intravenous bolus of glucose using the minimal model. The adequacy of the insulin secretory response in relation to the insulin sensitivity index will be estimated. Stable isotopes will be utilized to determine changes in glucose turnover. Glucose-insulin secretion dose-response relationship during exogenous glucose infusions that raise and then lower the plasma glucose concetration.