Brain GLP-1 and insulin sensitivity.
Brain GLP-1 and insulin sensitivity.
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DOI：
10.1016/j.mce.2015.02.017
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发表时间：
2015-12-15
影响因子：
4.1
通讯作者：
Sisley SR
中科院分区：
文献类型：
--
作者：
Sandoval D;Sisley SR
2型糖尿病通常用一类称为胰高血糖素样肽-1 （GLP-1）类似物的药物治疗。GLP-1是一种由肠道分泌的肽，仅通过一种已知受体GLP-1受体起作用。GLP-1的主要功能被认为是降低餐后血糖水平。事实上，利用这一系统的药物，包括长效GLP-1类似物利拉鲁肽和艾塞那肽，都有利于降低血糖和体重。长期以来，人们一直认为GLP-1类似物能够通过外周作用于β细胞而提高胰岛素水平，从而影响血糖控制。然而，多项数据表明，GLP-1能够在大脑中起作用，改变葡萄糖调节。在这篇综述中，我们将讨论中枢GLP-1系统的证据，以及大脑中GLP-1在调节葡萄糖稳态的多个方面的作用，包括葡萄糖耐量、胰岛素产生、胰岛素敏感性、肝脏葡萄糖产生、肌肉葡萄糖摄取以及中枢GLP-1系统与肠道的连接。尽管有证据表明大脑中的GLP-1受体对葡萄糖调节的生理控制不是必需的，但我们讨论了显示急性操纵中枢GLP-1系统对葡萄糖控制的强烈影响及其与2型糖尿病患者的关系的研究。
Type 2 diabetes is often treated with a class of drugs referred to as glucagon-like peptide-1 (GLP-1) analogs. GLP-1 is a peptide secreted by the gut that acts through only one known receptor, the GLP-1 receptor. The primary function of GLP-1 is thought to be lowering of postprandial glucose levels. Indeed, medications utilizing this system, including the long-acting GLP-1 analogs liraglutide and exenatide, are beneficial in reducing both blood sugars and body weight. GLP-1 analogs were long presumed to affect glucose control through their ability to increase insulin levels through peripheral action on beta cells. However, multiple lines of data point to the ability of GLP-1 to act within the brain to alter glucose regulation. In this review we will discuss the evidence for a central GLP-1 system and the effects of GLP-1 in the brain on regulating multiple facets of glucose homeostasis including glucose tolerance, insulin production, insulin sensitivity, hepatic glucose production, muscle glucose uptake, and connections of the central GLP-1 system to the gut. Although the evidence indicates that GLP-1 receptors in the brain are not necessary for physiologic control of glucose regulation, we discuss the research showing a strong effect of acute manipulation of the central GLP-1 system on glucose control and how it is relevant to type 2 diabetic patients.