There is a need to determine the conditions that will maximize the capacity of adult and neonatal islets to function as a viable graft in diabetic animals. Central to viability in avascular pancreatic grafts is revascularization. Therefore the primary aim of this project is to assess the role of basic fibroblast growth factor (FGF), an angiogenic protein, in pancreatic islet transplantation into normal and diabetic rats. This would be the first attempt to use this peptide, the most potent angiogenic mediator yet isolated, to promote revascularization. The hypothesis for this approach is that angiogenic mediators should significantly enhance graft performance. This hypothesis will be tested by showing the effects of FGF on islet blood flow, islet growth, and function in transplantation experiments. The expected beneficial effects of increased vascularization by FGF might be reflected in a substantial decrease in the number of neonatal or adult islets needed to cure diabetes.
The specific aims are: 1. To assess the effects of FGF in islet transplantation into normal rats on a) islet blood flow; b) islet growth; and c) islet function. 2. To assess the effects of FGF on islets transplanted into diabetic and insulin-treated diabetic rats. 3. To determine whether FGF lessens the number of transplanted adult or neonatal islets needed to cure experimental diabetes. Success with the use of exogenous angiogenic mediators will be measured by their ability to enhance function and to decrease the amount of purified endocrine replacement tissue needed for transplantation into diabetic recipients. Positive results in these experiments should be important to human diabetes.
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