Implantation Site–Dependent Dysfunction of Transplanted Pancreatic Islets

  1. Joey Lau1,
  2. Göran Mattsson1,
  3. Carina Carlsson1,
  4. Daniel Nyqvist2,
  5. Martin Köhler2,
  6. Per-Olof Berggren2,
  7. Leif Jansson1 and
  8. Per-Ola Carlsson13
  1. 1Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
  2. 2Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  1. Address correspondence and reprint requests to Joey Lau, Department of Medical Cell Biology, Biomedical Center, Husargatan 3, Box 571, Uppsala University, SE-751 23 Uppsala, Sweden. E-mail: joey.lau{at}mcb.uu.se

Abstract

OBJECTIVE—Clinical islet transplantations are performed through infusion of islets via the portal vein into the liver. This study aimed at characterizing the influence of the implantation microenvironment on islet graft metabolism and function.

RESEARCH DESIGN AND METHODS—Islets were transplanted into their normal environment, i.e., the pancreas, or intraportally into the liver of mice. One month posttransplantation, the transplanted islets were retrieved and investigated for changes in function and gene expression.

RESULTS—Insulin content, glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate were markedly decreased in islets retrieved from the liver, both when compared with islets transplanted into the pancreas and endogenous islets. Islets transplanted into the pancreas showed normal insulin content, (pro)insulin biosynthesis, and glucose oxidation rate but increased basal insulin secretion and impaired glucose stimulation index. Gene expression data for retrieved islets showed downregulation of pancreatic and duodenal homeobox gene-1, GLUT-2, glucokinase, mitochondrial glycerol-phosphate dehydrogenase, and pyruvate carboxylase, preferentially in intraportally transplanted islets.

CONCLUSIONS—Islets transplanted into their normal microenvironment, i.e., the pancreas, display gene expression changes when compared with endogenous islets but only moderate changes in metabolic functions. In contrast, site-specific properties of the liver markedly impaired the metabolic functions of intraportally transplanted islets.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 30 March 2007. DOI: 10.2337/db06-1258.

  • J.L. and G.M. contributed equally to this work.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 18, 2007.
    • Received September 7, 2006.
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  1. Published online before print March 30, 2007, doi: 10.2337/db06-1258 Diabetes June 2007 vol. 56 no. 6 1544-1550
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