The GLP-1 receptor agonist, exenatide, has previously been shown to improve insulin secretion, protect beta cells from apoptosis, and promote beta cell regeneration. We propose that pretreatment with exenatide will promote islet graft survival and improve graft function. Pancreatectomized cynomolgus monkeys underwent islet allotransplantation and were treated with exenatide beginning on day 0 or day ？2. A third group of animals was treated with an immunosuppressive regimen while a fourth group remained untreated. Fasting blood glucose (FBG) was used to evaluate graft function along with intravenous glucose tolerance tests (IVGTTs) performed at study endpoint (day 10 for untreated and posttransplant exenatide or day 90 for pretreatment exenatide and immunosuppression). The average FBG for pre-treated animals day 5 following transplant was ？mg/dl, compared to ？mg/dl for animals treated only following transplant, 59.4？mg/dl for animals treated with immunosuppression, and ？mg/dl for untreated animals. IVGTTs performed at study endpoint showed normal glucose and insulin curves in the pre-treated exenatide and immunosuppression groups only, with beta cell function actually improving after transplant in the pre-treated group. We conclude, therefore, that exenatide pre-treatment can successfully maintain islet graft survival in nonhuman primates. 1. Introduction Traditionally, type 1 diabetes has been treated by either life-long insulin therapy or, in severe cases, pancreas transplantation. However, frequent episodes of hypoglycemia are common in patients on life-long insulin therapy, and whole pancreas transplantation is an invasive surgical procedure with significant risks. Islet cell transplantation is an attractive alternative to these traditional treatments. However, two of the major limiting factors in the widespread use of islet cell transplantation clinically are the availability of a sufficient number of islets and the inability of current immunosuppressive treatments to protect transplanted islets in the long term. As of 2010, an estimated 1.5 million people in the United States were diagnosed with insulin-dependent diabetes [1]. According to a 2011 report by the US Department of Health and Human Services, Organ Procurement and Transplantation Network, only 1,562 pancreatic donors were reported [2]. Because islet transplantation is still an experimental procedure, priority of donor pancreata goes to whole organ transplant, thus limiting the potential donors available for islet transplantation. In addition to this already limited availability of
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