title: 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 5-20 mM, whereas superoxide generation was maximal at 0-1 mM glucose. Superoxide generation started rapidly (15-30 min) 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.
authors: Department of Cell Physiology and Metabolism, Medical Faculty, University of Geneva, Geneva, Switzerland. alexandre.sarre@chuv.ch
authors: Alexandre
authors: A
authors: Sarre
authors: Jessica
authors: J
authors: Gabrielli
authors: Guillaume
authors: G
authors: Vial
authors: Xavier M
authors: XM
authors: Leverve
authors: Françoise
authors: F
authors: Assimacopoulos-Jeannet
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000154:Aconitate Hydratase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D002460:Cell Line; D003997:Dicarbethoxydihydrocollidine / Q000031:analogs & derivatives / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000009:adverse effects*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008665:Metalloporphyrins / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D012402:Rotenone / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D008665:Metalloporphyrins; D008689:Methacrylates; D017382:Reactive Oxygen Species; D013844:Thiazoles; C514241:dihydroethidine; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D012402:Rotenone; D013481:Superoxides; C028404:rotenolone; D000249:Adenosine Monophosphate; D003997:Dicarbethoxydihydrocollidine; C030517:myxothiazol; D013482:Superoxide Dismutase; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D000154:Aconitate Hydratase; D042967:Electron Transport Complex I; D005947:Glucose