Acute Insulin Response to Arginine in Deceased Donors Predicts the Outcome of Human Islet Isolation

Abstract

Despite a stringent donor selection, human islet isolation remains frustratingly unpredictable. In this study, we measured acute insulin response to arginine (AIRarg), an in vivo surrogate measure of islet mass, in 29 human deceased donors before organ donation, and correlated values with the outcome of islet isolation. Thirteen isolations (45%) met the threshold for clinical islet transplantation. Among all measured donor characteristics, the only discriminating variable between successful or unsuccessful isolations was donor AIRarg (p < 0.01). Using a threshold of 55 lIU/mL (ROC curve AUC: 72%), isolation was successful in 12/19 donors with high AIRarg and in 1/10 donors with low AIRarg (p < 0.001). The negative and positive predictive values were 90 and 63%, respectively. If used to select donors in the entire cohort, AIRarg would have increased our success rate by 40% and avoided 56% of unsuccessful isolations while missing only 8% of successful preparations. Our results suggest that donor AIRarg is markedly superior to body mass index (BMI) and other criteria currently used to predict isolation outcome. If routinely performed in deceased donors, this simple test could significantly reduce the failure rate of human islet isolation.Key words: Donor evaluation, donor screening, donor selection, insulin secretion, islet isolation, islet transplantation Abbreviations: AIRarg, acute insulin response to arginine; IEQ, islet-equivalents; AUC, area under curve; BMI, body mass index.

Primary Graft Function, Metabolic Control, and Graft Survival After Islet Transplantation

“…Islets were isolated from ABO-compatible deceased donor pancreata with a negative cross-match and evaluated as previously described (8). The access to the portal vein was gained under general anesthesia by percutaneous catheterization of a peripheral portal branch under ultrasound guidance or by surgical catheterization of a small mesenteric vein.…”

Predicting the outcome of islet isolation in large mammals

“…Exploring this hypothesis in large mammalian models, we indeed confirmed that the main determinant of islet isolation outcome is the donor islet mass itself. In two studies, in the pig [5] and in humans [6], the pancreatic endocrine mass was assessed by determination of the acute insulin response (AIR) [7] in the donor. Stimulation by injection of arginine is preferred in human organ donors because it does not affect glycaemia and does not interfere with the functioning of other organs, whereas glucose can be used as an alternative in experimental studies, as employed in our pig model [5].…”

Stimulation of insulin secretion by large-dose oral arginine administration in healthy adults

“…Floyd et al first identified that intravenous arginine administration increases the insulin concentration in the blood circulation (16). Thus, the intravenous arginine load test is clinically used as the non-glucose promoting secretion test to evaluate the function of islet β-cells in patients with T2DM (17-20), leading to the exploration of the oral arginine load test.…”