Diabetologia

, Volume 43, Issue 6, pp 763–772

Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA and uPAR, TGF-α, TGF-β, bFGF and Vimentin) in cultured and transplanted rat islets

  • B. Vasir
  • P. Reitz
  • G. Xu
  • A. Sharma
  • S. Bonner-Weir
  • G. C. Weir

DOI: 10.1007/s001250051374

Cite this article as:
Vasir, B., Reitz, P., Xu, G. et al. Diabetologia (2000) 43: 763. doi:10.1007/s001250051374

Abstract

Aims/hypothesis. The vascularisation of newly transplanted islets originates from the recipients. Because islets transplanted into a diabetic do less well than those transplanted into a euglycaemic environment, we examined the hypothesis that gene expression of angiogenic factors in grafts is delayed in diabetes. These factors include hepatocyte growth factor (HGF) and its receptor c-MET, and urokinase plasminogen activator (uPA) and its receptor uPAR, basic fibroblast growth factor (bFGF), TGF-α and TGFβ-1.¶Methods. Isolated rat islets were studied in vitro under normoxic and hypoxic culture conditions and gene expression was determined with semi-quantitative multiplex RT-PCR. We found that HGF but not c-MET expression was induced by hypoxia in vitro. Using syngeneic Lewis rats, gene expression was also studied in grafts on days 1, 3, 5, 7 and 14 after transplantation.¶Results. In grafts of normoglycaemic rats, HGF expression was enhanced on day 3 and maintained whereas expression of c-MET fell and remained down until day 14. Expression of uPA was up at day 3 and remained high; expression of uPAR was also up at day 3 but then fell to control levels at day 14. Expression of bFGF, TGF-α and TGFβ-1 persisted throughout. Vimentin, a marker of fibroblasts, had increased expression at day 1 which was further enhanced in subsequent days. In the grafts of diabetic recipients the expression of HGF, uPA and uPAR were delayed, being clearly expressed at day 5 rather than day 3. Vimentin expression was similarly delayed.¶Conclusion/interpretation. This apparent delay in angiogenesis provides a potential mechanism for the less favourable outcomes of islets transplanted into diabetic recipients. [Diabetologia (2000) 43: 763–772]

Keywords Diabetes, islet transplantation, angiogenesis, hepatocyte growth factor and c-MET receptor and urokinase plasminogen activator, bFGF, TGF-β, TGF-α.
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© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • B. Vasir
    • 1
  • P. Reitz
    • 1
  • G. Xu
    • 1
  • A. Sharma
    • 1
  • S. Bonner-Weir
    • 1
  • G. C. Weir
    • 1
  1. 1.Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USAUS