Reactive oxygen species are produced at low glucose and contribute to the activation of AMPK in insulin-secreting cells. - Archive ouverte HAL Access content directly
Journal Articles Free Radical Biology and Medicine Year : 2011

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

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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.

Dates and versions

inserm-00641809 , version 1 (16-11-2011)

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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, 2011, epub ahead of print. ⟨10.1016/j.freeradbiomed.2011.10.437⟩. ⟨inserm-00641809⟩

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