Reactive oxygen species are produced at low glucose and contribute to the activation of AMPK in insulin-secreting cells.

Abstract : Excess reactive oxygen species (ROS) production is thought to play a key role in the loss of pancreatic β-cell number and/or function, in response to high glucose and/or fatty acids. However, contradictory findings have been reported showing that in pancreatic β cells or insulin-secreting cell lines, ROS are produced under conditions of either high or low glucose. Superoxide production was measured in attached INS1E cells as a function of glucose concentration, by following in real time the oxidation of dihydroethidine. Minimal values of superoxide production were measured at glucose concentrations of 5-20mM, whereas superoxide generation was maximal at 0-1mM glucose. Superoxide generation started rapidly (15-30min) after exposure to low glucose and was suppressed by its addition within minutes. Superoxide was totally suppressed by rotenone, but not myxothiazol, suggesting a role for complex I in this process. Indirect evidence for mitochondrial ROS generation was also provided by a decrease in aconitase activity. Activation of AMPK, a cellular metabolic sensor, and its downstream target ACC by low glucose concentration was largely inhibited by addition of MnTBAP, a MnSOD and catalase mimetic that also totally suppressed superoxide production. Taken together, the data show that low glucose activates AMPK in a superoxide-dependent, AMP-independent way.
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Free Radical Biology and Medicine, Elsevier, 2011, epub ahead of print. 〈10.1016/j.freeradbiomed.2011.10.437〉
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Soumis le : mercredi 16 novembre 2011 - 16:40:10
Dernière modification le : mardi 10 octobre 2017 - 09:24:05

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Alexandre Sarre, Jessica Gabrielli, Guillaume Vial, Xavier M Leverve, Françoise Assimacopoulos-Jeannet. Reactive oxygen species are produced at low glucose and contribute to the activation of AMPK in insulin-secreting cells.. Free Radical Biology and Medicine, Elsevier, 2011, epub ahead of print. 〈10.1016/j.freeradbiomed.2011.10.437〉. 〈inserm-00641809〉

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