The Islet Isolation and Transplantation Core will provide Project Investigators with a reliable supply of isolated mouse pancreatic islets for use in transplantation. Mouse islets will be prepared by the personnel of the Core. Core personnel will also perform all islet transplantation surgery. The need for this Core was recognized in our two previous proposals, and our laboratory has supported the activities of an Islet Isolation Core since 1991. The need for the core is determined by both biological and logistical considerations. Islets comprise <1% of the mass of the pancreas, are distributed nearly uniformly throughout a gland laden with digestive enzymes, and are fixed in position by a network ofvasculature and fibrous tissue. Their isolation is a time-consuming procedure that requires considerable skill. On average, each mouse transplant recipient requires all the islets that can be obtained from about four donors. In our experience, one technician can process enough donors to transplant 3 to 4 chemically diabetic mice per day. Each mouse requires 20 islets per gram of body weight to restore normoglycemia. After an isolation is complete, Core personnel will also be responsible for the transplantation of islets using aseptic technique into the renal sub-capsular space of recipients. Projections made by Program Project investigators indicate that approximately 500 islet isolation and transplantation procedures will be needed yearly. One technician engaged in islet isolation at 60% time will be required to satisfy projected needs.