Recovery of endogenous beta-cell function in nonhuman primates after chemical diabetes induction and islet transplantation.

Abstract

To describe the ability of nonhuman primate endocrine pancreata to reestablish endogenous insulin production after chemical beta-cell destruction. Eleven monkeys (Macaca fascicularis) were rendered diabetic with streptozotocin. Eight diabetic monkeys received intraportal porcine islet transplantation. Two monkeys transplanted after 75 days of type 1 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 costained with proinsulin and PDX-1 antibodies. Furthermore, the peculiar double phenotype glucagon-positive/GLUT2(+) was observed. In these monkeys as well as in all others, the original islets showed no insulin staining. Our data provide evidence that, in nonhuman primates, the pancreas can reestablish endogenous insulin production after chemical beta-cell destruction. This seems to be a nongeneralizable event with only 2 out of 11 monkeys recovering beta-cell function. In these two monkeys, younger age and islet graft behavior might have played a role in triggering endogenous beta-cell recovery.