This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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