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

  1. Bottino Rita (rib16{at}pitt.edu)1,
  2. Criscimanna Angela1,2,
  3. Casu Anna1,
  4. He Jing1,
  5. Dirk J Van der Windt1,
  6. William A Rudert1,
  7. Carla Giordano2 and
  8. Massimo Trucco1
  1. 1Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213. USA
  2. 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

      • Received August 19, 2008.
      • Accepted November 1, 2008.

    This Article

    1. Diabetes November 10, 2008
    1. » Abstract
    2. All Versions of this Article:
      1. db08-1127v1
      2. db08-1127v2
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