PANCREAS AND ISLET TRANSPLANTATION IN HUMANS

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"The overall goal of the work described in this proposal is to fully understand the metabolic consequences of long term, successful pancreas and islet transplantation in Type 1 Diabetic patients and to ascertain the long term metabolic consequences of hemi pancreatectomy in healthy human donors. For recipients of pancreas transplantation, the two specific aims are: Specific Aim 1: To compare insulin secretory reserve in pancreas transplant recipients receiving either cyclosporin or FK 506 as immunosuppressive therapy. Specific Aim 2: To assess counter- regulatory responses of glucagon and epinephrine during hypoglycemic, hyperinsulinemic clamps pretransplant and longitudinally posttransplant and to ascertain whether differences in responses exist in patients receiving cyclosporin or FK506. For normal patients who have undergone hemi pancreatectomy to donate hemi organs to relatives, the two specific aims are Specific Aim 3: To assess glycemic regulation and insulin secretory reserve pre operatively and longitudinally post operatively in donors. Specific Aim 4: To assess insulin mediated glucose disposal, glucose mediated glucose disposal, and glycemic regulation pre operatively and longitudinally post operatively in healthy human donors. For type 1 patients receiving auto or allotransplantation of islets, the three specific aims are: Specific Aim 5: To correlate measurements of post transplant insulin secretory reserve with the number of islets autotransplanted in non diabetic chronic pancreatitis patients. Specific Aim 6: To compare glycemic regulation and insulin secretory reserve longitudinally in islet recipients receiving steroids or no steroid and cyclosporin or FK 506. Specific Aim 7: To assess glucagon responses during hypoglycemic, hyperinsulinemic clamps pre operatively and longitudinally in type 1 diabetic patients receiving alloislets. The research design and methods for achieving these goals will include measurements of glucose and hemoglobin AlC levels; insulin, C peptide, and glucagon secretion; hypoglycemic, hyperinsulinemic and euglycemic, hyperinsulinemic (with and without concurrent somatostatin infusion) clamps; and studies of glucose potentiation of arginine induced insulin secretion."