Abstract
BackgroundIncreased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid (ALA) has been indicated as a weight-loss treatment in rodents and humans, but studies are limited. In the present study, we aimed to determine the influence of ALA, a potent biological antioxidant, on metabolic and growth processes in diabetic rat skeletal muscle.MethodsMale 25-week-old type 2 diabetic rats (OLETF) were randomly divided into two groups, a control group (OLETF-C) and an ALA-treated group (OLETF-ALA) supplemented with 100 mg/kg ALA for 8 weeks. Age-matched, healthy, nondiabetic LETO (LETO-C) rats were used as controls.ResultsAt 32 weeks of age, body weight was decreased by 6.8%, and the areas under the curve of IP-GTT, fasting glucose, and insulin were less in OLETF-ALA rats compared with OLETF-C rats. ALA significantly preserved muscle mass and enhanced muscle fiber cross-sectional area and fiber frequency percentage in the skeletal muscle of OLETF rats. Although the activation of myoD, myogenin, and myostatin in gastrocnemius muscle was significantly inhibited in OLETF-ALA rats relative to OLETF-C rats, there were no differences in the expression levels of muscle atrogin-1 and MuRF1 between the two groups. ALA treatment significantly increased the levels of phosphorylated 5′-AMPK, SIRT1, and PGC-1α, as well as the levels of phosphorylated AKT, mTOR, and p70S6 kinase in OLETF-ALA rats compared with OLETF-C rats. In contrast, the levels of phosphorylated p38 MAPK, IRS-1, and FOXO1 were decreased in OLETF-ALA rats compared with OLETF-C rats.ConclusionsALA treatment preserved mass in the gastrocnemius muscles of OLETF rats. ALA significantly upregulated the AMPK/SIRT1/PGC-1α and AKT/mTOR/p70S6K signaling pathways in OLETF rat skeletal muscle. Therefore, ALA may be a potential therapeutic intervention for skeletal muscle loss in animal models of insulin resistance.
Highlights
Increased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy
Body weight was significantly increased in Otsuka Long-Evans Tokushima Fatty (OLETF)-C rats compared with OLETF-Alpha-lipoic acid (ALA) rats at the end of the treatment period (653.3 ± 7.9 g vs. 611.8 ± 7.9 g, respectively; P < 0.05), as ALA prevented body weight increase in OLETF rats (Fig. 1a)
OLETF-C rats displayed marked and significant increases in fed plasma glucose levels relative to OLETF-ALA rats (P < 0.05, Fig. 1b), daily food intake for the duration of the feeding trial did not differ between the two groups (Fig. 1c and d)
Summary
Increased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid (ALA) has been indicated as a weight-loss treatment in rodents and humans, but studies are limited. We aimed to determine the influence of ALA, a potent biological antioxidant, on metabolic and growth processes in diabetic rat skeletal muscle. Skeletal muscle comprises approximately 40% of total body weight and contains 50–75% of all body proteins [1]. Alpha-lipoic acid (ALA) is a sulfur-containing coenzyme involved in mitochondrial dehydrogenase reactions leading to adenosine triphosphate (ATP) formation [6]. The beneficial effects of ALA in diabetes have long been recognized, and are mainly attributed to its involvement in glycemic control, increasing antioxidant markers, and
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