Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis
Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis
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DOI：
10.1159/000455865
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发表时间：
2017-01-01
影响因子：
4.1
通讯作者：
Cowley, Michael A.
中科院分区：
文献类型：
--
作者：
Chen, Weiyi;Balland, Eglantine;Cowley, Michael A.
肥胖和2型糖尿病之间的中心联系是胰岛素抵抗的发展。迄今为止，尚不清楚高胰岛素血症是否会导致胰岛素抵抗，而胰岛素抵抗是肥胖相关的2型糖尿病发病机制的基础，因为外周和大脑中存在复杂的调节机制。近年来，越来越多的证据表明下丘脑存在胰岛素抵抗。在这篇综述中，我们已经整合了最近的发现围绕中枢和外周胰岛素抵抗，提供一个全面的概述肥胖和全身葡萄糖稳态的调节胰岛素抵抗。特别是，这篇综述将讨论如何高胰岛素血症和高瘦素血症的肥胖损害胰岛素敏感性的组织，如肝脏，骨骼肌，脂肪组织和大脑。此外，这篇综述强调了胰岛素转运到大脑中，与下丘脑胰岛素受体表达相关的信号通路在肝脏葡萄糖产生的调节，最后全身葡萄糖稳态的扰动作为中枢胰岛素抵抗的结果。我们还建议未来的方法来克服中枢和外周胰岛素抵抗治疗肥胖和2型糖尿病。(C)2017 S. Karger AG，巴塞尔
The central link between obesity and type 2 diabetes is the development of insulin resistance. To date, it is still not clear whether hyperinsulinemia causes insulin resistance, which underlies the pathogenesis of obesity-associated type 2 diabetes, owing to the sophisticated regulatory mechanisms that exist in the periphery and in the brain. In recent years, accumulating evidence has demonstrated the existence of insulin resistance within the hypothalamus. In this review, we have integrated the recent discoveries surrounding both central and peripheral insulin resistance to provide a comprehensive overview of insulin resistance in obesity and the regulation of systemic glucose homeostasis. In particular, this review will discuss how hyperinsulinemia and hyperleptinemia in obesity impair insulin sensitivity in tissues such as the liver, skeletal muscle, adipose tissue, and the brain. In addition, this review highlights insulin transport into the brain, signaling pathways associated with hypothalamic insulin receptor expression in the regulation of hepatic glucose production, and finally the perturbation of systemic glucose homeostasis as a consequence of central insulin resistance. We also suggest future approaches to overcome both central and peripheral insulin resistance to treat obesity and type 2 diabetes. (C) 2017 S. Karger AG, Basel