caa a22 4500 475771117 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s001250051374 doi (NATIONALLICENCE)springer-10.1007/s001250051374 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 [Elektronische Daten] [B. Vasir, P. Reitz, G. Xu, A. Sharma, S. Bonner-Weir, G. C. Weir] 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] Springer-Verlag Berlin Heidelberg, 2000 Keywords Diabetes, islet transplantation, angiogenesis, hepatocyte growth factor and c-MET receptor and urokinase plasminogen activator, bFGF, TGF-β, TGF-α nationallicence Vasir B. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut Reitz P. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut Xu G. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut Sharma A. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut Bonner-Weir S. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut Weir G. C. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut https://doi.org/10.1007/s001250051374 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051374 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Vasir B. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut NATIONALLICENCE 700 1- Reitz P. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut NATIONALLICENCE 700 1- Xu G. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut NATIONALLICENCE 700 1- Sharma A. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut NATIONALLICENCE 700 1- Bonner-Weir S. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut NATIONALLICENCE 700 1- Weir G. C. Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer