Recovery of endogenous beta cell function in non-human primates following chemical diabetes induction and islet transplantation
- Bottino Rita (rib16{at}pitt.edu)1,
- Criscimanna Angela1,2,
- Casu Anna1,
- He Jing1,
- Dirk J Van der Windt1,
- William A Rudert1,
- Carla Giordano2 and
- Massimo Trucco1
- 1Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213. USA
- 2Division of Endocrinology, DOSAC, Universita' degli Studi di Palermo, Palermo, Italy
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.
Results: 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.
Footnotes
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- Received August 19, 2008.
- Accepted November 1, 2008.
- Copyright © American Diabetes Association











