Transient beneficial effects of exendin-4 treatment on the function of microencapsulated mouse pancreatic islets

Transplantation of microencapsulated islets may reduce hyperglycemia in the absence of immunosuppression. However, the efficiency of microencapsulated islet transplantation is low, requiring more islets to achieve normoglycemia than in vascularized islet transplantation. Exendin-4 (a glucagon-like receptor agonist) has been previously shown to improve islet transplantation outcome in rodents. We investigated whether this treatment would enhance the function of microencapsulated islets in vitro and in vivo. Encapsulated or naked islets were cultured with or without exendin-4 for 72 h. To test in vitro function, insulin release and glucose oxidation rates were measured in the absence or presence of exendin-4. In addition, in vivo function of a minimal mass of 350 microencapsulated islets was assessed by syngeneic transplantation into the peritoneal cavity of alloxan-diabetic mice. Glucose oxidation rates of microencapsulated islets were improved by 72-h pretreatment with exendin-4. Insulin release was increased both acutely after glucose stimulation and over a 40-h culture period by the presence of exendin-4. Transplantation outcome of microencapsulated islets cultured with exendin-4 was initially improved, but by day 7 there were no differences compared with control cultured microencapsulated islets. Culture of microencapsulated islets with exendin-4 increases glucose oxidation and insulin release rates, but the increased function seen in vitro was not enough to improve the long term outcome in a transplantation model.