The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
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DOI：
10.1073/pnas.0705408104
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发表时间：
2007-07-31
影响因子：
11.1
通讯作者：
Shulman, Gerald I.
中科院分区：
文献类型：
--
作者：
Petersen, Kitt Falk;Dufour, Sylvie;Shulman, Gerald I.
我们研究了骨骼肌中的胰岛素抵抗通过改变餐后能量储存的分布模式，促进与代谢综合征相关的动脉粥样硬化性血脂异常的发展的假设。在摄入两份高碳水化合物混合餐后，年轻、瘦弱、胰岛素抵抗的受试者的净肌糖原合成与年龄-体重-体重-活性匹配、胰岛素敏感的对照组受试者相比减少了约60%。相比之下，胰岛素抵抗者的肝脏新生、脂肪生成和肝脏甘油三酯合成均增加了150倍。这些变化与血浆甘油三酯浓度增加60%，血浆高密度脂蛋白浓度降低约20%有关，但血浆tnf - α、IL-6、脂联素、抵抗素、视黄醇结合蛋白-4或腹内脂肪量的浓度没有差异。这些数据表明，由于肌糖原合成减少，骨骼肌中的胰岛素抵抗可以通过改变摄入碳水化合物的模式，从骨骼肌糖原合成转变为肝脏新生脂肪生成，从而促进动脉粥样硬化性血脂异常，导致血浆甘油三酯浓度升高，血浆高密度脂蛋白浓度降低。此外，这些受试者的胰岛素抵抗与血浆中tnf - α、IL-6、高分子量脂联素、抵抗素、视黄醇结合蛋白-4或腹内肥胖浓度的变化无关，这表明这些因素在代谢综合征早期引起胰岛素抵抗的过程中并不起主要作用。
We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribution pattern of postprandial energy storage. Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthesis was reduced by approximate to 60% in young, lean, insulin-resistant subjects compared with a similar cohort of age-weight-body mass inclex-activity- matched, insulin-sensitive, control subjects. In contrast, hepatic de novo, lipogenesis and hepatic triglyceride synthesis were both increased by > 2-fold in the insulin-resistant subjects. These changes were associated with a 60% increase in plasma triglyceride concentrations and an approximate to 20% reduction in plasma high-density lipoprotein concentrations but no differences in plasma concentrations of TNF-alpha, IL-6, adiponectin, resistin, retinol binding protein-4, or intraabdominal fat volume. These data demonstrate that insulin resistance in skeletal muscle, due to decreased muscle glycogen synthesis, can promote atherogenic dyslipidemia by changing the pattern of ingested carbohydrate away from skeletal muscle glycogen synthesis into hepatic de novo lipogenesis, resulting in an increase in plasma triglyceride concentrations and a reduction in plasma high-density lipoprotein concentrations. Furthermore, insulin resistance in these subjects was independent of changes in the plasma concentrations of TNF-alpha, IL-6, high-molecular-weight adiponectin, resistin, retinol binding protein-4, or intraabdominal obesity, suggesting that these factors do not play a primary role in causing insulin resistance in the early stages of the metabolic syndrome.