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[神经酰胺,胰岛素抵抗和2型糖尿病发展中的关键因素]

[Ceramides, crucial actors in the development of insulin resistance and type 2 diabetes].

作者信息

Tan-Chen Sophie, Bourron Olivier, Hajduch Éric

机构信息

Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, 18 rue de l'École de Médecine, F-75006 Paris, France - Institut Hospitalo-Universitaire ICAN, Paris, France.

Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, 18 rue de l'École de Médecine, F-75006 Paris, France - Institut Hospitalo-Universitaire ICAN, Paris, France - Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service de Diabétologie et Maladies Métaboliques, Hôpital Pitié-Salpêtrière, 75013 Paris, France.

出版信息

Med Sci (Paris). 2020 May;36(5):497-503. doi: 10.1051/medsci/2020091. Epub 2020 May 26.

Abstract

In healthy subjects, the balance between glucose production and its usage is precisely controlled. When circulating glucose reaches a critical threshold, pancreatic β-cells secrete insulin, which has two major actions: lowering circulating glucose concentrations by facilitating its uptake mainly in skeletal muscles and the liver, and inhibiting glucose production. Triglycerides are the main source of fatty acids to meet the energy needs of oxidative tissues and any excess is stored in adipocytes. Thus, adipose tissue acts as a trap for excess fatty acids released from plasma triglycerides. When the buffering action of adipose tissue to store fatty acids is impaired, they accumulate in other tissues where they are metabolized in several lipid species, including sphingolipid derivatives such as ceramides. Numerous studies have shown that ceramides are among the most active lipid second messengers to inhibit insulin signalling. This review describes the major role played by ceramides in the development of insulin resistance in peripheral tissues.

摘要

在健康受试者中,葡萄糖生成与利用之间的平衡受到精确调控。当循环葡萄糖达到临界阈值时,胰腺β细胞分泌胰岛素,胰岛素有两个主要作用:通过促进葡萄糖主要在骨骼肌和肝脏中的摄取来降低循环葡萄糖浓度,并抑制葡萄糖生成。甘油三酯是满足氧化组织能量需求的脂肪酸的主要来源,任何多余的部分都储存在脂肪细胞中。因此,脂肪组织充当了从血浆甘油三酯中释放的多余脂肪酸的储存库。当脂肪组织储存脂肪酸的缓冲作用受损时,脂肪酸会在其他组织中积累,并在那里代谢为多种脂质,包括神经酰胺等鞘脂衍生物。大量研究表明,神经酰胺是抑制胰岛素信号传导的最活跃的脂质第二信使之一。本综述描述了神经酰胺在周围组织胰岛素抵抗发展中所起的主要作用。

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