PROJECT SUMMARY / ABSTRACT Human pancreatic islets are an essential research resource for research on the prevention, treatment, and pathophysiology of diabetes mellitus. Recent data have highlighted important differences between murine and human islets, substantiating the continued need for access to human islets, as the gold standard in diabetes research. City of Hope (COH) is applying for this U24 renewal to remain as the Integrated Islet Distribution Program Coordinating Center (IIDP CC) for the next 5 years, to continue to provide distribution of human cadaveric islets and ancillary tissue for biomedical research to researchers worldwide. Our proposal leverages the significant investment made by NIH over the last 19 years that has established and successfully maintained the IIDP at COH. From qualification and auditing of high-quality Islet Isolation Centers (IICs), to forecasting, tracking, and meeting the needs of investigators, since 2002 our experienced team has worked with 20 different islet isolation laboratories to coordinate the distribution of over 330 million islet equivalents to more than 400 investigators across 16 countries since 2002, supporting 767 peer reviewed publications. Through this renewal we will continue to subcontract with our 5 highly qualified IICs to isolate and distribute human islets and ancillary tissue via our advanced electronic Islet Allocation System (IAS). We will continue to manage the review process for islet receipt, pilot studies, and Opportunity Pool funding. We will further enhance our IAS to broadcast offers online and notify approved waiting researchers of islet availability, in a fair, equitable and time sensitive manner. IIDP will continue to maintain the existing cost recovery system through subscription fees collected from islet researchers, which has garnered a total of $9,303,950 since the implementation of subscription fees to offset the expenses of pancreatic processing for the IICs. We will continue to closely monitor and help to improve the quality of islets distributed, through the continuation of the Human Islet Phenotyping Program (HIPP) that conducts assays on a sample from each islet isolation. IIDP has just added a Human Islet Genotyping Initiative (HIGI) to genotype each isolation as well. Phenotyping and genotyping data, as well as UNOS data, extensive donor and islet isolation data, will be made available to approved investigators through online access to the IIDP Research Data Repository, with IIDP and NIDDK approval of applying scientists. Investigators can easily search the required data, select filter criteria, save their searches, and download the integrated IIDP data for exploratory analyses. Through our proven state-of-the-art administrative, business, technical, statistical, quality assurance, and informatics processes and tools, the accessibility of human islets for investigators conducting essential diabetes mellitus research will be secured. We will continue to provide ...