Skeletal muscle insulin resistance: the interplay of local lipid excess and mitochondrial dysfunction.
Skeletal muscle insulin resistance: the interplay of local lipid excess and mitochondrial dysfunction.
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DOI：
10.1016/j.metabol.2009.07.009
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发表时间：
2010-01
影响因子：
9.8
通讯作者：
Seaquist, Elizabeth
中科院分区：
文献类型：
--
作者：
Chow, Lisa;From, Arthur;Seaquist, Elizabeth
2型糖尿病（DM 2）的患病率由于人口老龄化和肥胖流行而急剧增加。2型糖尿病的特征是胰腺β细胞功能障碍和多个组织中的胰岛素抵抗，这些异常先于并预测DM 2的发展[1，2]。骨骼肌占外周组织中胰岛素介导的葡萄糖摄取的大部分[3，4]。因此，了解骨骼肌中胰岛素抵抗发生的机制可能为治疗或预防DM 2提供潜在的治疗方法。骨骼肌脂质代谢异常和线粒体功能障碍被认为是骨骼肌胰岛素抵抗的可能机制[5]。在多项针对未经训练受试者的研究中，肌细胞内脂质（IMCL）升高与胰岛素抵抗相关[6-8]。脂质输注在游离脂肪酸（FFA）升高后数小时诱导胰岛素抵抗[9，10]。在人类中，胰岛素抵抗与线粒体功能减弱[8，11，12]，氧化代谢基因表达减少[13，14]，线粒体大小减少[15]和线粒体密度减少[15]有关。本综述的目的是探讨局部脂质暴露，线粒体功能障碍，以及人体骨骼肌水平的胰岛素抵抗。重点将放在人类研究上，尽管选择的动物和基于细胞的研究将被介绍，以获得对病理生理学的更详细的见解。我们开始与胰岛素介导的葡萄糖处置和相关的正常生理学的简要概述
The prevalence of type 2 diabetes mellitus (DM2) is increasing precipitously as a consequence of the aging population and obesity epidemic. Type 2 diabetes mellitus is characterized by both pancreatic β-cell dysfunction and insulin resistance in multiple tissues, abnormalities that precede and predict the development of DM2 [1, 2]. Skeletal muscle accounts for the majority of insulin-mediated glucose uptake in peripheral tissue [3, 4]. Thus, understanding the mechanism by which insulin resistance develops in skeletal muscle may offer insight into potential therapies for the treatment or prevention of DM2. Abnormalities in skeletal muscle lipid metabolism and mitochondrial dysfunction have been proposed as possible mechanisms for skeletal muscle insulin resistance [5]. In multiple studies of untrained subjects, elevation of intramyocellular lipid (IMCL) correlates with insulin resistance [6-8]. Lipid infusion induces insulin resistance several hours after free fatty acid (FFA) elevation [9, 10]. In humans, insulin resistance has been associated with diminished mitochondrial function [8, 11, 12], reduced expression of oxidative metabolism genes [13, 14], decreased mitochondrial size [15], and reduced mitochondrial density [15].The purpose of this review is to explore the complex relationship between local lipid exposure, mitochondrial dysfunction, and insulin resistance at the level of human skeletal muscle. The focus will be on human studies, although selected animal and cell-based studies will be presented for more detailed insights into pathophysiology. We begin with a brief overview of the normal physiology of insulin-mediated glucose disposal and the associated
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影响因子：
15.9
作者：
Bonnard, Charlotte;Durand, Annie;Rieusset, Jennifer
通讯作者：
Rieusset, Jennifer
影响因子：
64.8
作者：
BURGERING, BMT;COFFER, PJ
通讯作者：
COFFER, PJ
影响因子：
7.7
作者：
Bao, S;Kennedy, A;Garvey, WT
通讯作者：
Garvey, WT
DOI：
10.1152/ajpendo.90287.2008
发表时间：
2008-09-01
影响因子：
5.1
作者：
Abdul-Ghani, Muhammad A.;Muller, Florian L.;DeFronzo, Ralph A.
通讯作者：
DeFronzo, Ralph A.
影响因子：
7.7
作者：
Bajaj, M;Suraamornkul, S;DeFronzo, RA
通讯作者：
DeFronzo, RA