Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes
Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes
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DOI：
10.2337/db07-0141
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发表时间：
2007-08-01
期刊：
影响因子：
7.7
通讯作者：
Kelley, David E.
中科院分区：
文献类型：
--
作者：
Toledo, Frederico G. S.;Menshikova, Elizabeta V.;Kelley, David E.
目的：骨骼肌线粒体容量降低发生在2型糖尿病患者和这种疾病的高风险人群中，但通过体力活动和减肥干预，2型糖尿病患者的线粒体功能障碍在多大程度上是可以补救的还不确定。我们试图解决日常中等强度运动结合适度减肥的干预是否可以增加2型糖尿病患者骨骼肌线粒体的含量，以及与改善胰岛素抵抗和高血糖的关系。研究设计和方法-在干预4个月之前和之后获取肌肉活组织以评估线粒体形态、线粒体DNA含量和线粒体酶活性。结果：体重下降了7.1+/-0.8%，最大摄氧量提高了12+/-1.6%(P<；0.05)，胰岛素敏感性提高了59+/-21%(P<；0.05)。骨骼肌线粒体密度显著增加(67+/-17%，P<；0.01)，心磷脂含量(55+/-17%，P<；0.01)和线粒体氧化酶显著增加。体力活动时的能量消耗与胰岛素敏感性的改善程度相关(r=0.84，P<；0.01)，而线粒体含量的改善又与干预诱导的A1C和空腹血糖的改善密切相关。结论强化的短期生活方式改变可以恢复2型糖尿病患者骨骼肌中线粒体的含量和功能。骨骼肌氧化能力的改善可能是生活方式干预对高血糖和胰岛素抵抗的有益影响的关键组成部分。
Objective-Reduced mitochondrial capacity in skeletal muscle occurs in type 2 diabetic patients and in those at increased risk for this disorder, but the extent to which mitochondrial dysfunction in type 2 diabetic patients is remediable by physical activity and weight loss intervention is uncertain. We sought to address whether an intervention of daily moderate-intensity exercise combined with moderate weight loss can increase skeletal muscle mitochondrial content in type 2 diabetic patients and to address the relationship with amelioration of insulin resistance and hyperglycemia.Research design and methods-Muscle biopsies were obtained before and after a 4-month intervention to assess mitochondrial morphology, mitochondrial DNA content, and mitochondrial enzyme activities. Glucose control, body composition, aerobic fitness, and insulin sensitivity were measured.Results-In response to a weight loss of 7.1 +/- 0.8% and a 12 +/- 1.6% improvement in VO2max (P < 0.05), insulin sensitivity improved by 59 +/- 21% (P < 0.05). There were significant increases in skeletal muscle mitochondrial density (by 67 +/- 17%, P < 0.01), cardiolipin content (55 +/- 17%, P < 0.01), and mitochondrial oxidation enzymes. Energy expenditure during physical activity correlated with the degree of improvement in insulin sensitivity (r = 0.84, P < 0.01), and, in turn, improvement in mitochondrial content was a strong correlate of intervention- induced improvement in A1C and fasting plasma glucose.Conclusions-Intensive short-term lifestyle modifications can restore mitochondrial content and functional capacity in skeletal muscle in type 2 diabetic patients. The improvement in the oxidative capacity of skeletal muscle may be a key component mediating salutary effects of lifestyle interventions on hyperglycemia and insulin resistance.