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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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https://www.hal.inserm.fr/inserm-00641809
Contributor : Sarah Hamant <>
Submitted on : Wednesday, November 16, 2011 - 4:40:10 PM
Last modification on : Wednesday, July 15, 2020 - 9:10:03 AM

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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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