Recovery of endogenous beta cell function in non-human primates following chemical diabetes induction and islet transplantation

Abstract

Objectives: To describe the ability of non-human primate endocrine pancreata to re-establish endogenous insulin production after chemical beta cell destruction. Research Design and Methods: Eleven monkeys (macaca fascicularis) were rendered diabetic with streptozotocin. Eight diabetic monkeys received intraportal porcine islet transplantation. Results: Two monkeys transplanted after 75 days of insulin dependent diabetes, showed recovery of endogenous C-peptide production a few weeks after transplantation, concomitant with graft failure. Histological analysis of the pancreas of these monkeys showed insulin-positive cells, single or in small aggregates scattered in the pancreas and adjacent to ducts. Interestingly, numerous CK19+ cells co-stained with proinsulin and PDX-1 antibodies. Furthermore, the peculiar double phenotype glucagon+/GLUT2+ was observed. In these monkeys as well as in all others the original islets showed no insulin staining. Conclusions: Our data provide evidence that in non-human primates the pancreas can re-establish endogenous insulin production after chemical beta cell destruction. This seems to be a non-generalizable event with only two out of eleven monkeys recovering beta cell function. In these two monkeys, younger age and islet graft behaviour might have played a role in triggering endogenous beta cell recovery.