Journal article
Metformin Selectively Attenuates Mitochondrial H2O2 Emission without Affecting Respiratory Capacity in Skeletal Muscle of Obese Rats
Free radical biology & medicine, Vol.49(6), pp.1082-1087
09/15/2010
DOI: 10.1016/j.freeradbiomed.2010.06.022
PMCID: PMC2921476
PMID: 20600832
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
2
flux and H
2
O
2
emission were measured in saponin-permeabilized myofibers from lean and obese (
fa/fa
) Zucker rats treated for 4 wks with metformin. Succinate- and palmitoyl-carnitine- supported respiration generated >2-fold higher rates of H
2
O
2
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
2
O
2
emission in muscle from obese rats to rates near or below those observed in lean rats during both succinate- and palmitoyl-carnitine- supported respiration. Surprisingly, metformin treatment did not affect basal or maximal rates of O
2
consumption in muscle from obese or lean rats.
Ex vivo
dose-response experiments revealed that metformin inhibits complex I-linked H
2
O
2
emission at a concentration ∼2 orders of magnitude lower than that required to inhibit respiratory O
2
flux. These findings suggest that therapeutic concentrations of metformin normalize mitochondrial H
2
O
2
emission by blocking reverse electron flow without affecting forward electron flow or respiratory O
2
flux in skeletal muscle.
Details
- Title: Subtitle
- Metformin Selectively Attenuates Mitochondrial H2O2 Emission without Affecting Respiratory Capacity in Skeletal Muscle of Obese Rats
- Creators
- Daniel A Kane - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North CarolinaEthan J Anderson - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North CarolinaJesse W Price - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North CarolinaTracey L Woodlief - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North CarolinaChien-Te Lin - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North CarolinaBenjamin T Bikman - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North CarolinaRonald N Cortright - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North CarolinaP. Darrell Neufer - East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.49(6), pp.1082-1087
- DOI
- 10.1016/j.freeradbiomed.2010.06.022
- PMID
- 20600832
- PMCID
- PMC2921476
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Language
- English
- Date published
- 09/15/2010
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984065313502771
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