文献DOI：10.1186/s12986-018-0302-y
文献PMID：30275871
文献原文链接：http://doi.org.sci-hub.tw/10.1186/s12986-018-0302-y
Alpha-lipoic acid preserves skeletal muscle mass in type 2 diabetic OLETF rats
α-硫辛酸保留2型糖尿病OLETF大鼠中骨骼肌质量的研究
【Abstract】
Background: 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. 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.
Methods: Male 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.
Results: At 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.
Conclusions: ALA 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.
Keywords: Alpha-lipoic acid, Diabetic rat, Diabetes mellitus, Skeletal muscle, Muscle mass
摘要翻译：
背景：氧化应激增加和抗氧化防御受损是糖尿病肌病的重要发病机制。 α-硫辛酸（ALA）已被指示为啮齿动物和人类的减肥治疗，但研究有限。在本研究中，我们旨在确定ALA（一种有效的生物抗氧化剂）对糖尿病大鼠骨骼肌代谢和生长过程的影响。
方法：将25周龄雄性2型糖尿病大鼠（OLETF）随机分为两组，对照组（OLETF-C）和ALA治疗组（OLETF-ALA），补充100 mg / kg ALA，共8周。用年龄匹配的、健康的、非糖尿病的LETO（LETO-C）大鼠用作对照。
结果：与OLETF-C大鼠相比，OLETF-ALA大鼠32周龄时体重下降6.8％，IP-GTT、空腹血糖和胰岛素曲线下面积减少。 ALA显著保留了OLETF大鼠骨骼肌的肌肉质量，增强了肌纤维横截面积和纤维频率百分比。尽管OLETF-ALA大鼠相对于OLETF-C大鼠的腓肠肌中myoD、肌细胞生成素和肌肉生长抑制素的激活受到显著抑制，但两组间肌肉atrogin-1和MuRF1的表达水平没有差异。与OLETF-C大鼠相比，ALA处理显著增加了OLETF-ALA大鼠中磷酸化的5'-AMPK、SIRT1和PGC-1α的水平，以及磷酸化的AKT、mTOR和p70S6激酶的水平。相反，与OLETF-C大鼠相比，OLETF-ALA大鼠中磷酸化的p38MAPK，IRS-1和FOXO1的水平降低。
结论：ALA治疗可以保护OLETF大鼠腓肠肌的质量。 ALA显著上调OLETF大鼠骨骼肌中的AMPK / SIRT1 / PGC-1α和AKT / mTOR / p70S6K信号传导途径。因此，ALA可能是胰岛素抵抗动物模型中骨骼肌损失的潜在治疗干预。
关键词：α-硫辛酸，糖尿病大鼠，糖尿病，骨骼肌，肌肉质量