Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany; Department of Internal Medicine IV, University of Tübingen, Tübingen, Germany; Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany; and Department of Pharmacy and Biochemistry, Faculty of Science, Eberhard Karls Universität Tübingen, Tübingen, Germany.
Physiol Rev. 2016 Oct;96(4):1169-209. doi: 10.1152/physrev.00032.2015. Epub 2016 Aug 3.
Ever since the brain was identified as an insulin-sensitive organ, evidence has rapidly accumulated that insulin action in the brain produces multiple behavioral and metabolic effects, influencing eating behavior, peripheral metabolism, and cognition. Disturbances in brain insulin action can be observed in obesity and type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin sensitivity of central nervous pathways, i.e., brain insulin resistance, may therefore constitute a joint pathological feature of metabolic and cognitive dysfunctions. Modern neuroimaging methods have provided new means of probing brain insulin action, revealing the influence of insulin on both global and regional brain function. In this review, we highlight recent findings on brain insulin action in humans and its impact on metabolism and cognition. Furthermore, we elaborate on the most prominent factors associated with brain insulin resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging, inflammation, and dementia, and on their roles regarding causes and consequences of brain insulin resistance. We also describe the beneficial effects of enhanced brain insulin signaling on human eating behavior and cognition and discuss potential applications in the treatment of metabolic and cognitive disorders.
自从大脑被确认为对胰岛素敏感的器官以来，越来越多的证据表明，大脑中的胰岛素作用会产生多种行为和代谢效应，影响进食行为、外周代谢和认知。肥胖症和 2 型糖尿病（T2D）以及衰老和痴呆症患者中均可观察到大脑胰岛素作用的紊乱。中枢神经通路的胰岛素敏感性降低，即大脑胰岛素抵抗，可能因此构成代谢和认知功能障碍的共同病理特征。现代神经影像学方法为研究大脑胰岛素作用提供了新的手段，揭示了胰岛素对大脑整体和区域功能的影响。在这篇综述中，我们重点介绍了人类大脑胰岛素作用的最新发现及其对代谢和认知的影响。此外，我们详细阐述了与大脑胰岛素抵抗相关的最主要因素，即肥胖症、T2D、基因、母体代谢、正常衰老、炎症和痴呆症，并讨论了它们在大脑胰岛素抵抗的原因和后果中的作用。我们还描述了增强大脑胰岛素信号对人类进食行为和认知的有益影响，并讨论了在治疗代谢和认知障碍方面的潜在应用。
