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胰岛素在大脑中的作用调节中枢和外周功能。

Insulin action in the brain regulates both central and peripheral functions.

机构信息

Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah.

Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah.

出版信息

Am J Physiol Endocrinol Metab. 2021 Jul 1;321(1):E156-E163. doi: 10.1152/ajpendo.00642.2020. Epub 2021 May 31.

Abstract

The brain has been traditionally thought to be insensitive to insulin, primarily because insulin does not stimulate glucose uptake/metabolism in the brain (as it does in classic insulin-sensitive tissues such as muscle, liver, and fat). However, over the past 20 years, research in this field has identified unique actions of insulin in the brain. There is accumulating evidence that insulin crosses into the brain and regulates central nervous system functions such as feeding, depression, and cognitive behavior. In addition, insulin acts in the brain to regulate systemic functions such as hepatic glucose production, lipolysis, lipogenesis, reproductive competence, and the sympathoadrenal response to hypoglycemia. Decrements in brain insulin action (or brain insulin resistance) can be observed in obesity, type 2 diabetes (T2DM), aging, and Alzheimer's disease (AD), indicating a possible link between metabolic and cognitive health. Here, we describe recent findings on the pleiotropic actions of insulin in the brain and highlight the precise sites, specific neuronal population, and roles for supportive astrocytic cells through which insulin acts in the brain. In addition, we also discuss how boosting brain insulin action could be a therapeutic option for people at an increased risk of developing metabolic and cognitive diseases such as AD and T2DM. Overall, this perspective article serves to highlight some of these key scientific findings, identify unresolved issues, and indicate future directions of research in this field that would serve to improve the lives of people with metabolic and cognitive dysfunctions.

摘要

传统上认为大脑对胰岛素不敏感,主要是因为胰岛素不会像在肌肉、肝脏和脂肪等经典胰岛素敏感组织中那样刺激大脑中的葡萄糖摄取/代谢。然而,在过去的 20 年中,该领域的研究已经确定了胰岛素在大脑中的独特作用。越来越多的证据表明,胰岛素进入大脑并调节摄食、抑郁和认知行为等中枢神经系统功能。此外,胰岛素在大脑中作用于调节全身功能,如肝葡萄糖生成、脂肪分解、脂肪生成、生殖能力和低血糖时的交感肾上腺反应。在肥胖、2 型糖尿病 (T2DM)、衰老和阿尔茨海默病 (AD) 中可以观察到大脑胰岛素作用的降低(或大脑胰岛素抵抗),这表明代谢和认知健康之间可能存在联系。在这里,我们描述了胰岛素在大脑中的多效作用的最新发现,并强调了胰岛素在大脑中作用的确切部位、特定神经元群体和支持性星形胶质细胞的作用。此外,我们还讨论了如何增强大脑胰岛素作用可能成为代谢和认知疾病(如 AD 和 T2DM)风险增加人群的治疗选择。总的来说,这篇观点文章旨在强调这些关键科学发现中的一些,确定未解决的问题,并指出该领域未来的研究方向,以改善代谢和认知功能障碍人群的生活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/460e/8321819/5672c6a1000f/e-00642-2020r01.jpg

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