Acute insulin response of donors is correlated with pancreatic islet isolation outcome in the pig

Aims/hypothesis Unpredictability of islet isolation outcome remains a frustrating and costly issue in the clinical implementation of islet transplantation. The aim of this experimental study was to test the hypothesis that the donors insulin secretory reserve, an in vivo surrogate of functional pancreatic mass, is correlated with the outcome of islet isolation.Methods Insulin secretory reserve was evaluated in 28 healthy adult minipigs prior to pancreatectomy and islet isolation. Blood glucose and insulinaemia were measured before and 1, 3, 5, 10, 15, 30, 60 and 90 min after glucose infusion. Following total pancreatectomy, islet isolation was performed according to Ricordis semi-automated method, and the total number of islets obtained was determined. Fasting blood glucose, insulinaemia, acute insulin response (AIR), maximal insulinaemia and the glucose decay constant (K_G) were calculated, and possible associations with the outcome of islet isolation were assessed.Results AIR and maximal insulinaemia after glucose injection were correlated with the outcome of islet isolation (p<0.01). Mean values for AIR and maximal insulinaemia were significantly different between animals in which islet isolation was successful (n=11) vs those in which it was unsuccessful (n=17) (77.6±13.7 U/ml vs 42.3±7.8 U/ml, p<0.05; 144.7±21.6 U/ml vs 71.9±10.4 U/ml, p<0.05, respectively).Conclusions/interpretation This study suggests that the donors pancreatic endocrine mass, as estimated by AIR, is a major determinant of the outcome of islet isolation in large mammals. Our results may explain the frustrating variability of human islet isolation outcome and could lead to a new approach for optimising the selection of brain-dead and/or living pancreas donors.