کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1909866 1046743 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metformin selectively attenuates mitochondrial H2O2 emission without affecting respiratory capacity in skeletal muscle of obese rats
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Metformin selectively attenuates mitochondrial H2O2 emission without affecting respiratory capacity in skeletal muscle of obese rats
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 49, Issue 6, 15 September 2010, Pages 1082–1087
نویسندگان
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