Wei Yongzhong, Chen Kemin, Whaley-Connell Adam T, Stump Craig S, Ibdah Jamal A, Sowers James R
Department of Internal Medicine, University of Missouri School of Medicine, Columbia, Missouri 65212, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R673-80. doi: 10.1152/ajpregu.00561.2007. Epub 2007 Dec 19.
The cardiometabolic syndrome (CMS), with its increased risk for cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and chronic kidney disease (CKD), has become a growing worldwide health problem. Insulin resistance is a key factor for the development of the CMS and is strongly related to obesity, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), CKD, and NAFLD. Insulin resistance in skeletal muscle is particularly important since it is normally responsible for more than 75% of all insulin-mediated glucose disposal. However, the molecular mechanisms responsible for skeletal muscle insulin resistance remain poorly defined. Accumulating evidence indicates that low-grade chronic inflammation and oxidative stress play fundamental roles in the development of insulin resistance, and inflammatory cytokines likely contribute to the link between inflammation, oxidative stress, and skeletal muscle insulin resistance. Understanding the mechanisms by which skeletal muscle tissue develops resistance to insulin will provide attractive targets for interventions, which may ultimately curb this serious problem. This review is focused on the effects of inflammatory cytokines and oxidative stress on insulin signaling in skeletal muscle and consequent development of insulin resistance.
心脏代谢综合征（CMS）会增加心血管疾病（CVD）、非酒精性脂肪性肝病（NAFLD）和慢性肾脏病（CKD）的发病风险，已成为全球日益严重的健康问题。胰岛素抵抗是CMS发生发展的关键因素，与肥胖、高脂血症、高血压、2型糖尿病（T2DM）、CKD和NAFLD密切相关。骨骼肌中的胰岛素抵抗尤为重要，因为正常情况下，胰岛素介导的葡萄糖代谢超过75%由骨骼肌负责。然而，导致骨骼肌胰岛素抵抗的分子机制仍不清楚。越来越多的证据表明，低度慢性炎症和氧化应激在胰岛素抵抗的发生发展中起重要作用，炎症细胞因子可能在炎症、氧化应激与骨骼肌胰岛素抵抗之间的联系中发挥作用。了解骨骼肌组织产生胰岛素抵抗的机制将为干预提供有吸引力的靶点，最终可能遏制这一严重问题。本综述重点关注炎症细胞因子和氧化应激对骨骼肌胰岛素信号的影响以及随之而来的胰岛素抵抗的发生发展。
