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Master Thesis

Rôle du pore de transition de perméabilité mitochondriale dans l'apoptose des cellules béta pancréatiques

Abstract : Pancreatic β cells apoptosis in islet transplantation is a major problem: 50% of the graft is lost within fifteen days after transplantation due to nonspecific events (ischemia-reperfusion, glucotoxicity ...). Mitochondrial permeability transition pore (PTP) is a mitochondrial protein complex implicated in cell death. Pancreatic endocrine cells PTP regulation has so far never been explored. We studied PTP regulation in β cells mouse model (INS-1) and involvement of PTP in cell death induced by 30 mM D-glucose and 2.5 mM D-fructose on this type cell. We show that Cyclosporin A, reference inhibitor of PTP, and metformin inhibit PTP opening in permeabilized and intact INS-1 cells. In addition, we describe that INS-1 exposure to 30 mM D-glucose or 2.5 mM D-fructose induces PTP opening and increases in INS-1cell death. Finally, we show that cyclosporin A and Metformin, by inhibiting PTP opening, reduce cellular death induced by D-glucose and D-fructose. We conclude that D-glucose and D-fructose cytotoxicity passes through a PTP opening and cell death induced by D-glucose and D-fructose can be prevented by Cyclosporine A and Metformin through a PTP inhibition. Thus, targeting the PTP in transplantation of islets of Langerhans may be a useful strategy for preserving the viability of β cells during this procedure.
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Master Thesis
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Submitted on : Tuesday, October 11, 2011 - 2:59:32 PM
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  • HAL Id : dumas-00631109, version 1
  • PPN : 155577131


Sandrine Cornali Lablanche. Rôle du pore de transition de perméabilité mitochondriale dans l'apoptose des cellules béta pancréatiques. Médecine humaine et pathologie. 2009. ⟨dumas-00631109⟩



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