Difference between revisions of "Kane 2010 Free Radic Biol Med"
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{{Publication | {{Publication | ||
|title=Kane DA, Anderson EJ, Price III JW, Woodlief TL, Lin C-T, Bikman BT, Cortright RN, Neufer PD (2010) Metformin selectively attenuates mitochondrial H<sub>2</sub>O<sub>2</sub> emission without affecting respiratory capacity in skeletal muscle of obese rats. Free | |title=Kane DA, Anderson EJ, Price III JW, Woodlief TL, Lin C-T, Bikman BT, Cortright RN, Neufer PD (2010) Metformin selectively attenuates mitochondrial H<sub>2</sub>O<sub>2</sub> emission without affecting respiratory capacity in skeletal muscle of obese rats. Free Radic Biol Med 49: 1082–1087. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed | |info=[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921476/?tool=pubmed PMID: 20600832 Open Access] | ||
|authors=Kane DA, Anderson EJ, Price III JW, Woodlief TL, Lin CT, Bikman BT, Cortright RN, Neufer PD | |authors=Kane DA, Anderson EJ, Price III JW, Woodlief TL, Lin CT, Bikman BT, Cortright RN, Neufer PD | ||
|year=2010 | |year=2010 | ||
|journal=Free | |journal=Free Radic Biol Med | ||
|abstract=Metformin is a widely prescribed drug for treatment of type 2 diabetes, although no cellular mechanism of action has been established. To determine whether ''in vivo'' metformin treatment alters mitochondrial function in skeletal muscle, respiratory O<sub>2</sub> flux and H<sub>2</sub>O<sub>2</sub> emission were measured in saponin-permeabilized myofibers from lean and obese (fa/fa) Zucker rats treated for 4 weeks with metformin. Succinate- and palmitoylcarnitine-supported respiration generated greater than twofold higher rates of H<sub>2</sub>O<sub>2</sub> emission in myofibers from untreated obese versus lean rats, indicative of an obesity-associated increased mitochondrial oxidant emitting potential. In conjunction with improved glycemic control, metformin treatment reduced H<sub>2</sub>O<sub>2</sub> emission in muscle from obese rats to rates near or below those observed in lean rats during both succinate- and palmitoylcarnitine-supported respiration. Surprisingly, metformin treatment did not affect basal or maximal rates of O<sub>2</sub> consumption in muscle from obese or lean rats. ''Ex vivo'' dose–response experiments revealed that metformin inhibits complex I-linked H<sub>2</sub>O<sub>2</sub> emission at a concentration ~2 orders of magnitude lower than that required to inhibit respiratory O<sub>2</sub> flux. These findings suggest that therapeutic concentrations of metformin normalize mitochondrial H<sub>2</sub>O<sub>2</sub> emission by blocking reverse electron flow without affecting forward electron flow or respiratory O<sub>2</sub> flux in skeletal muscle. | |abstract=Metformin is a widely prescribed drug for treatment of type 2 diabetes, although no cellular mechanism of action has been established. To determine whether ''in vivo'' metformin treatment alters mitochondrial function in skeletal muscle, respiratory O<sub>2</sub> flux and H<sub>2</sub>O<sub>2</sub> emission were measured in saponin-permeabilized myofibers from lean and obese (fa/fa) Zucker rats treated for 4 weeks with metformin. Succinate- and palmitoylcarnitine-supported respiration generated greater than twofold higher rates of H<sub>2</sub>O<sub>2</sub> emission in myofibers from untreated obese versus lean rats, indicative of an obesity-associated increased mitochondrial oxidant emitting potential. In conjunction with improved glycemic control, metformin treatment reduced H<sub>2</sub>O<sub>2</sub> emission in muscle from obese rats to rates near or below those observed in lean rats during both succinate- and palmitoylcarnitine-supported respiration. Surprisingly, metformin treatment did not affect basal or maximal rates of O<sub>2</sub> consumption in muscle from obese or lean rats. ''Ex vivo'' dose–response experiments revealed that metformin inhibits complex I-linked H<sub>2</sub>O<sub>2</sub> emission at a concentration ~2 orders of magnitude lower than that required to inhibit respiratory O<sub>2</sub> flux. These findings suggest that therapeutic concentrations of metformin normalize mitochondrial H<sub>2</sub>O<sub>2</sub> emission by blocking reverse electron flow without affecting forward electron flow or respiratory O<sub>2</sub> flux in skeletal muscle. | ||
|keywords=Type 2 diabetes, Zucker rats, | |keywords=Type 2 diabetes, Zucker rats, | ||
|mipnetlab=US_NC Greenville_Neufer PD, CA_Antigonish_Kane DA, US NC Greenville Anderson EJ | |mipnetlab=US_NC Greenville_Neufer PD, CA_Antigonish_Kane DA, US NC Greenville Anderson EJ | ||
|discipline=Mitochondrial Physiology, Biomedicine | |discipline=Mitochondrial Physiology, Biomedicine | ||
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|couplingstates=LEAK, OXPHOS, ETS | |couplingstates=LEAK, OXPHOS, ETS | ||
|topics=Substrate; Glucose; TCA Cycle, Fatty Acid | |topics=Substrate; Glucose; TCA Cycle, Fatty Acid | ||
|discipline=Mitochondrial Physiology, Biomedicine | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} | ||
Revision as of 12:03, 17 August 2012
| Kane DA, Anderson EJ, Price III JW, Woodlief TL, Lin C-T, Bikman BT, Cortright RN, Neufer PD (2010) Metformin selectively attenuates mitochondrial H2O2 emission without affecting respiratory capacity in skeletal muscle of obese rats. Free Radic Biol Med 49: 1082–1087. |
Kane DA, Anderson EJ, Price III JW, Woodlief TL, Lin CT, Bikman BT, Cortright RN, Neufer PD (2010) Free Radic Biol Med
Abstract: Metformin is a widely prescribed drug for treatment of type 2 diabetes, although no cellular mechanism of action has been established. To determine whether in vivo metformin treatment alters mitochondrial function in skeletal muscle, respiratory O2 flux and H2O2 emission were measured in saponin-permeabilized myofibers from lean and obese (fa/fa) Zucker rats treated for 4 weeks with metformin. Succinate- and palmitoylcarnitine-supported respiration generated greater than twofold higher rates of H2O2 emission in myofibers from untreated obese versus lean rats, indicative of an obesity-associated increased mitochondrial oxidant emitting potential. In conjunction with improved glycemic control, metformin treatment reduced H2O2 emission in muscle from obese rats to rates near or below those observed in lean rats during both succinate- and palmitoylcarnitine-supported respiration. Surprisingly, metformin treatment did not affect basal or maximal rates of O2 consumption in muscle from obese or lean rats. Ex vivo dose–response experiments revealed that metformin inhibits complex I-linked H2O2 emission at a concentration ~2 orders of magnitude lower than that required to inhibit respiratory O2 flux. These findings suggest that therapeutic concentrations of metformin normalize mitochondrial H2O2 emission by blocking reverse electron flow without affecting forward electron flow or respiratory O2 flux in skeletal muscle. • Keywords: Type 2 diabetes, Zucker rats
• O2k-Network Lab: US_NC Greenville_Neufer PD, CA_Antigonish_Kane DA, US NC Greenville Anderson EJ
Labels:
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Rat Tissue;cell: Skeletal muscle
Regulation: Substrate; Glucose; TCA Cycle"Substrate; Glucose; TCA Cycle" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Fatty Acid"Fatty Acid" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
