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Respective effects of oxygen and energy substrate deprivation on beta cell viability

Lablanche, Sandrine
Cottet-Rousselle, Cécile
Argaud, Laurent
Laporte, Camille
Lamarche, Frédéric
Richard, Marie-Jeanne
Benhamou, Pierre-Yves
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Published in Biochimica et Biophysica Acta. 2015, vol. 1847, no. 6-7, p. 629-639
Abstract Deficit in oxygen and energetic substrates delivery is a key factor in islet loss during islet transplantation. Permeability transition pore (PTP) is a mitochondrial channel involved in cell death. We have studied the respective effects of oxygen and energy substrate deprivation on beta cell viability as well as the involvement of oxidative stress and PTP opening. Energy substrate deprivation for 1h followed by incubation in normal conditions led to a cyclosporin A (CsA)-sensitive-PTP-opening in INS-1 cells and human islets. Such a procedure dramatically decreased INS-1 cells viability except when transient removal of energy substrates was performed in anoxia, in the presence of antioxidant N-acetylcysteine (NAC) or when CsA or metformin inhibited PTP opening. Superoxide production increased during removal of energy substrates and increased again when normal energy substrates were restored. NAC, anoxia or metformin prevented the two phases of oxidative stress while CsA prevented the second one only. Hypoxia or anoxia alone did not induce oxidative stress, PTP opening or cell death. In conclusion, energy substrate deprivation leads to an oxidative stress followed by PTP opening, triggering beta cell death. Pharmacological prevention of PTP opening during islet transplantation may be a suitable option to improve islet survival and graft success.
Keywords AcetylcysteineAnimalsAnoxiaApoptosisCellsCulturedEnergy MetabolismFlow CytometryFree Radical ScavengersHumansHypoglycemic AgentsIslets of LangerhansMetforminMicroscopyConfocalMitochondriaMitochondrial Membrane Transport ProteinsOxidative StressOxygenRatsReactive Oxygen Species
PMID: 25868875
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Research group La transplantation d'îlots de Langerhans (623)
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LABLANCHE, Sandrine et al. Respective effects of oxygen and energy substrate deprivation on beta cell viability. In: Biochimica et Biophysica Acta, 2015, vol. 1847, n° 6-7, p. 629-639. doi: 10.1016/j.bbabio.2015.04.002 https://archive-ouverte.unige.ch/unige:72754

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Deposited on : 2015-05-21

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