Endothelial and endocrine alterations in diabetic pancreas. Role of angiopoietin-2 and thrombospondin-1
| Autor: | Calderari, Sophie, Chougnet, C., Clemessy, M., KEMPF, H., Corvol, P., Larger, E. |
|---|---|
| Přispěvatelé: | ProdInra, Migration, Angiogénèse embryonnaire et pathologique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), European Association for the Study of Diabetes (EASD). GBR., École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Diabetologia 45. Annual Meeting of the European Association for the Study of Diabetes 45. Annual Meeting of the European Association for the Study of Diabetes, European Association for the Study of Diabetes (EASD). GBR., Sep 2009, Vienne, Austria. 550 p |
| Popis: | International audience; In the events leading to type 2 diabetes, inadequate compensatory increase of the beta cells mass could be a direct consequence of vascular disease, either by endothelial dysfunction or secondary to defective secretion of angiogenic peptides by beta cells. To dissect the role of angiogenic process in the maintenance and growth of islets, we studied pancreatic chimeras, consisting of endocrine chick cells and murine endothelial cells, obtained by grafting embryonic chick pancreas in SCID mice. We analyzed angiogenesis during development of the pancreatic chimera and examined the impact of hyperglycemia on the vasculature of the pancreas. We then used an avian-specific retrovirus, the RCAS system, to over-express VEGF during pancreatic development. Materials and methods: Seven-week-old female SCID mice were made diabetic by a single intra-peritoneal injection of streptozotocin (160mg/kg). Embryonic chick pancreases (E14) were grafted under the kidney capsule of SCID mice and collected 14 days later. Pancreatic vasculature was analyzed by immunohistochemistry using nestin, a mouse-specific endothelial marker, and in situ hybridization with both mouse- and chick-specific VEGFR-2 probes. Expression of angiopoïetin-2 (Ang2), thrombospondin-1 (Tsp1) and VEGF was analyzed by in situ hybridization. To over-express VEGF, an avian-specific retrovirus RCAS carrying the gene encoding the VEGF (RCAS-VEGF) was prepared. Chick pancreases were infected in vitro with the RCAS-VEGF for 1 hour before graft. Mammalian cells were not susceptible to the RCAS infection. All analyzes were performed on n=5 animals. This study was carried out along the principles of laboratory animal care. Results: As compared to normoglycemia, hyperglycemia increased beta-cell density (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|