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

Diabetes. 2009 Feb;58(2):442-7. doi: 10.2337/db08-1127. Epub 2008 Nov 10.

Abstract

Objective: To describe the ability of nonhuman primate endocrine pancreata to reestablish 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 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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / surgery*
  • Haplorhini
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans Transplantation / methods*
  • Streptozocin
  • Swine

Substances

  • Insulin
  • Streptozocin