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在不肥胖的情况下,外周胰岛素敏感性和线粒体容量的种族差异。

Racial differences in peripheral insulin sensitivity and mitochondrial capacity in the absence of obesity.

机构信息

Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.

出版信息

J Clin Endocrinol Metab. 2014 Nov;99(11):4307-14. doi: 10.1210/jc.2014-2512. Epub 2014 Aug 8.

Abstract

CONTEXT

African-American women (AAW) have an increased risk of developing type 2 diabetes compared with Caucasian women (CW). Lower insulin sensitivity has been reported in AAW, but the reasons for this racial difference and the contributions of liver versus skeletal muscle are incompletely understood.

OBJECTIVE

We tested the hypothesis that young, nonobese AAW manifest lower insulin sensitivity specific to skeletal muscle, not liver, and is accompanied by lower skeletal muscle mitochondrial oxidative capacity.

PARTICIPANTS AND MAIN OUTCOME MEASURES

Twenty-two nonobese (body mass index 22.7 ± 3.1 kg/m(2)) AAW and 22 matched CW (body mass index 22.7 ± 3.1 kg/m(2)) underwent characterization of body composition, objectively assessed habitual physical activity, and insulin sensitivity with euglycemic clamps and stable-isotope tracers. Skeletal muscle biopsies were performed for lipid content, fiber typing, and mitochondrial measurements.

RESULTS

Peripheral insulin sensitivity was 26% lower in AAW (P < .01), but hepatic insulin sensitivity was similar between groups. Physical activity levels were similar between groups. Lower insulin sensitivity in AAW was not explained by total or central adiposity. Skeletal muscle triglyceride content was similar, but mitochondrial content was lower in AAW. Mitochondrial respiration was 24% lower in AAW and correlated with skeletal muscle insulin sensitivity (r = 0.33, P < .05).

CONCLUSION

When compared with CW, AAW have similar hepatic insulin sensitivity but a muscle phenotype characterized by both lower insulin sensitivity and lower mitochondrial oxidative capacity. These observations occur in the absence of obesity and are not explained by physical activity. The only factor associated with lower insulin sensitivity in AAW was mitochondrial oxidative capacity. Because exercise training improves both mitochondrial capacity and insulin sensitivity, we suggest that it may be of particular benefit as a strategy for diabetes prevention in AAW.

摘要

背景

与白人女性(CW)相比,非裔美国女性(AAW)患 2 型糖尿病的风险增加。据报道,AAW 的胰岛素敏感性较低,但造成这种种族差异的原因以及肝脏与骨骼肌的贡献尚不完全清楚。

目的

我们检验了这样一个假设,即年轻、非肥胖的 AAW 表现出骨骼肌而非肝脏的胰岛素敏感性降低,并且伴随着骨骼肌线粒体氧化能力降低。

参与者和主要观察指标

22 名非肥胖(体重指数 22.7 ± 3.1 kg/m²)的 AAW 和 22 名匹配的 CW(体重指数 22.7 ± 3.1 kg/m²)接受了身体成分特征描述、习惯性体力活动的客观评估以及通过正葡萄糖钳夹和稳定同位素示踪剂进行的胰岛素敏感性评估。进行骨骼肌活检以评估脂质含量、纤维分型和线粒体测量。

结果

AAW 的外周胰岛素敏感性低 26%(P <.01),但两组的肝胰岛素敏感性相似。两组的体力活动水平相似。AAW 较低的胰岛素敏感性不能用总脂肪或中心脂肪来解释。AAW 的骨骼肌甘油三酯含量相似,但线粒体含量较低。AAW 的线粒体呼吸降低了 24%,与骨骼肌胰岛素敏感性相关(r = 0.33,P <.05)。

结论

与 CW 相比,AAW 具有相似的肝胰岛素敏感性,但肌肉表型的特点是胰岛素敏感性降低和线粒体氧化能力降低。这些观察结果发生在没有肥胖的情况下,并且不能用体力活动来解释。唯一与 AAW 较低胰岛素敏感性相关的因素是线粒体氧化能力。由于运动训练可提高线粒体能力和胰岛素敏感性,我们建议,对于 AAW 的糖尿病预防策略,运动训练可能特别有益。

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