Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University, Partners in the German Centre for Diabetes Research (DZD), Otfried-Müller-Street 10, 72076 Tübingen, Germany.
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Partners in the German Centre for Diabetes Research (DZD), Otfried-Müller-Street 10, 72076 Tübingen, Germany.
Nat Rev Endocrinol. 2015 Dec;11(12):701-11. doi: 10.1038/nrendo.2015.173. Epub 2015 Oct 13.
Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.
在过去的几年中，有越来越多的证据表明人类大脑是一个对胰岛素敏感的器官。胰岛素调节着大脑中有限数量的特定区域的活动，这些区域对记忆、奖励、进食行为和全身代谢的调节都很重要。因此，大脑中的胰岛素可以调节认知、食物摄入和体重以及全身的葡萄糖、能量和脂质代谢。然而，脑成像研究表明，并非每个人对胰岛素的反应都一样，而且相当一部分人存在大脑胰岛素抵抗。在这篇综述中，我们概述了胰岛素在人类大脑中的作用以及这些作用对生理学的重要性。我们提出了人类大脑胰岛素抵抗的新证据。我们回顾了与大脑胰岛素抵抗相关的因素，如肥胖和年龄增长，以及可能的致病因素，如内脏脂肪、饱和脂肪酸、血脑屏障的改变和某些遗传多态性。特别讨论了大脑胰岛素抵抗的代谢后果，并概述了未来克服大脑胰岛素抵抗以预防或治疗肥胖和 2 型糖尿病的可能方法。
