Defect of insulin signal in peripheral tissues: important role of ceramide  

作　　者：Rima Hage Hassan Olivier Bourron Eric Hajduch 

机构地区：[1]INSERM,UMR-S 1138,Centre de Recherche des Cordeliers,F-75006 Paris,France [2]UniversitéPierre et Marie Curie-Paris 6,UMR-S 872,F-75006 Paris,France [3]Université Paris Descartes,UMR-S 872,F-75006 Paris,France Olivier Bourron,Department de Diabétologie et Maladies métaboliques,AP-HP,Hopital Pitié-Salpêtrière,F-75006 Paris,France

出　　处：《World Journal of Diabetes》2014年第3期244-257,共14页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by INSERM,the SociétéFrancophone du Diabète;an Agence Nationale de la Recherche grant project(Crisalis)

摘　　要：In healthy people,balance between glucose production and its utilization is precisely controlled.When circulating glucose reaches a critical threshold level,pancreaticβcells secrete insulin that has two major actions:to lower circulating glucose levels by facilitating its uptake mainly into skeletal muscle while inhibiting its production by the liver.Interestingly,dietary triglycerides are the main source of fatty acids to fulfill energy needs of oxidative tissues.Normally,the unconsumed fraction of excess of fatty acids is stored in lipid droplets that are localized in adipocytes to provide energy during fasting periods.Thus,adipose tissue acts as a trap for fatty acid excess liberated from plasma triglycerides.When the buffering action of adipose tissue to store fatty acids is impaired,fatty acids that build up in othertissues are metabolized as sphingolipid derivatives such as ceramides.Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway.In healthy people,balance between glucose production and its utilization is precisely controlled.When circulating glucose reaches a critical threshold level,pancreaticβcells secrete insulin that has two major actions:to lower circulating glucose levels by facilitating its uptake mainly into skeletal muscle while inhibiting its production by the liver.Interestingly,dietary triglycerides are the main source of fatty acids to fulfill energy needs of oxidative tissues.Normally,the unconsumed fraction of excess of fatty acids is stored in lipid droplets that are localized in adipocytes to provide energy during fasting periods.Thus,adipose tissue acts as a trap for fatty acid excess liberated from plasma triglycerides.When the buffering action of adipose tissue to store fatty acids is impaired,fatty acids that build up in othertissues are metabolized as sphingolipid derivatives such as ceramides.Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway.

关 键 词：Diabetes Insulin resistance LIPIDS Insulin signaling TRIGLYCERIDES PALMITATE SPHINGOLIPID Akt Ceramide synthase Protein phosphatase 2A Protein kinase C ζ/λ 

分 类 号：R587.1[医药卫生—内分泌]