犬尿氨酸途径与2型糖尿病相关性研究进展

Research progress in the relevance of kynurenine pathway to type 2 diabetes mellitus

2型糖尿病(type 2 diabetes mellitus,T2DM)是由胰岛素抵抗和(或)胰岛素分泌相对不足引起的,以持续性高血糖为主要特征的一种糖、脂、蛋白质代谢紊乱性的慢性炎症性疾病,占全部糖尿病的90%以上。色氨酸可通过犬尿氨酸途径(kynurenine pathway,KP)、血清素(5-羟色胺)途径和肠道微生物(吲哚)途径在机体内进行分解代谢。近年来,大量研究发现,色氨酸代谢特别是KP的代谢异常可能影响T2DM的发生与发展。本文从KP及KP代谢物的生理病理作用、KP的代谢过程、KP代谢产物及参与该途径代谢的关键酶在T2DM中的变化情况、KP在T2DM病理机制中的作用以及通过调控KP来改善或延缓T2DM进展的具体策略等方面进行综述,以调节KP为新的切入点为T2DM提供可能的防治思路。

Type 2 diabetes mellitus(T2DM)is a chronic inflammatory disorder of glucose-lipid-protein metabolism disease,which is mainly characterised by persistent hyperglycaemia caused by insulin resistance and/or relative deficiency of insulin secretion,accounting for more than 90%of all diabetes mellitus.Tryptophan can be catabolised in the body through three pathways:the kynurenine pathway(KP),the serotonin(5-hydroxytryptamine)pathway and the gut microbial(indole)pathway.In recent years,a large number of studies have revealed that abnormalities in tryptophan metabolism,especially in the metabolism of KP,which is the most important one,may affect the onset and development of T2DM.This paper reviews the physiopathological roles of KP and KP metabolites,the metabolic process of KP,the changes of KP metabolites and key enzymes involved in the metabolism of this pathway in T2DM,the role of KP in the pathological mechanisms of T2DM,and the specific strategies for ameliorating or delaying the progression of T2DM through the modulation of KP,so that the regulation of KP as a novel entry point to provide a possible prevention and treatment of T2DM.