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

Abstract

OBJECTIVE-To describe the ability of nonhuman primate endocrine pancreata to reestablish endogenous insulin production after chemical β-cell destruction. RESEARCH DESIGN AND METHODS-Eleven monkeys (Macaca fascicularis) were rendered diabetic with streptozoto-cin. Eight diabetic monkeys received intraportal porcine islet transplantation. RESULTS-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. CONCLUSIONS-Our data provide evidence that, in nonhuman primates, the pancreas can reestablish endogenous insulin production after chemical β-cell destruction. This seems to be a nongeneralizable event with only 2 out of 11 monkeys recovering β-cell function. In these two monkeys, younger age and islet graft behavior might have played a role in triggering endogenous β-cell recovery. © 2009 by the American Diabetes Association.