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Genre/Form: | Thèses et écrits académiques |
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Material Type: | Document, Thesis/dissertation |
Document Type: | Computer File |
All Authors / Contributors: |
Fanny Guez ; sous la direction de Raphaël Scharfmann. ; Fanny Guez; Raphaël Scharfmann; Vincent Goffin; Selim Aractingi; Bertrand Blondeau; Christophe Magnan; Frank Yates, auteur d'une theÌse de doctorat en immunologie).; Université Paris Descartes (1970-2019).; École doctorale Génétique, cellulaire, immunologie, infectiologie et développement (Paris / ....-2013). |
OCLC Number: | 881300574 |
Notes: | Thèse soutenue sur un ensemble de travaux. Titre provenant de l'écran-titre. |
Description: | 1 online resource |
Contents: | Human beta cell replication and cell cycle regulation / Guez, Fanny, Rachdi, Latif, Scharfmann, Raphaël. -- , . -- Fetal pancreas transplants are dependent on prolactin for their development and prevent type 1 diabetes in syngeneic but not allogeneic mice / Fourcade, Gwladys, Colombo, Bruno M., Grégoire, Sylvie, Baeyens, Audrey, Rachdi, Latif, Guez, Fanny, Goffin, Vincent, Scharfmann, Raphael, Salomon, Benoît L.. -- Diabetes, 2013. -- Dyrk1a haploinsufficiency induces diabetes through decreased beta cell mass / Rachdi, Latif, Kariyawasam, Dulanjalee, Guez, Fanny, Aïello, Virginie, Arbonés, Maria L., Janel, Nathalie, Delabar, Jean-Maurice, Polak, Michel, Scharfmann, Raphaël. -- , . |
Abstract:
Diabetes is a disease that affects 347 million people worldwide (90% with type 2 diabetes) (WHO, September 2012). It is defined by a disturbance in the regulation of glucose homeostasis with a deficit in function of pancreatic beta cells. In type 1 diabetes, this deficit is caused by autoimmune destruction. In type 2 diabetes, it is due to peripheral insulin resistance leading to a depletion of beta cells that can no longer maintain their function. A strategy to restore a functional beta cell mass is, or of inducing proliferation of these cells in vitro prior to transplant, or to induce proliferation in vivo. However, this implies a better understanding of the molecular mechanisms involved in the cell cycle of human pancreatic beta cells. The aim of my thesis was to dissect these mechanisms. For this, we have a unique laboratory tool, two lines of human pancreatic beta cells. In one of them, immortalizing transgenes may be deleted. Then, the cells stop to proliferate giving pseudo- primary beta-cells. By comparing the expression of cell cycle regulators of the lineage of human beta cells immortalized pseudo- primary human beta- cells, we could show that the cycle of these cells was blocked in the G1 phase. The lack of several proteins responsible for cell cycle progression downstream of this phase has been confirmed in human islets. We also observed a decrease in the doubling time of human beta cells following treatment with GH and EPO. Following this treatment we also observe an activation of the transcription factor STAT5 known for its involvement in cell proliferation of rodent beta cells. Finally, we studied the effect that caused a nutrient supply on the function and proliferation of human beta cells. We have seen that the cells responded better to beta function with a doubling time shorter amount of cells in a nutrient enriched environment. In addition, under these conditions, autophagy, existing before the supply of nutrients and likely due to a lack of cellular energy, disappears. These results allow us to better understand the mechanisms controlling proliferation of human pancreatic ß and consider new diabetes therapies cells.
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