中医药调控AMPK信号通路防治肥胖2型糖尿病的研究进展

Prevention and Treatment of Obesity Type 2 Diabetes Mellitus by Traditional Chinese Medicine Through AMPK Signaling Pathway:A Review

肥胖合并2型糖尿病(T2DM)增加了胰岛素抵抗(IR)及代谢异常程度,显著增加了心脏病、癌症等疾病患病风险,其特征是IR和营养过剩。磷酸腺苷活化蛋白激酶(AMPK)作为代谢调节中心,主要响应细胞内丝氨酸/苏氨酸激酶-腺苷一磷酸(AMP)水平的变化,其激活后将细胞代谢模式从合成转换为分解以提高能量代谢,作用于炎症、缺血、肥胖和衰老等病理状态。近年来大量研究发现,AMPK为治疗肥胖T2DM的重要靶点,中药单体/提取物、中药复方通过调控AMPK信号通路主要影响哺乳动物雷帕霉素靶蛋白(mTOR)、沉默调节蛋白1(SIRT1)、核转录因子E2相关因子2(Nrf2)和核转录因子-κB(NF-κB)等关键信号因子,从而实现调节代谢、自噬、降低氧化应激和炎症反应等多种作用治疗肥胖T2DM,具有多靶点、全方位、低毒性等优势。中医药调控AMPK通路防治肥胖T2DM成为当今及未来的重要研究方向,但此领域尚无系统总结与归纳。该文总结了AMPK信号通路的构成与调控及其影响肥胖T2DM的机制,对中医药调控AMPK信号通路防治肥胖T2DM的研究现状作一综述,以期对肥胖T2DM的中医诊治及新药研发提供参考。

Obesity type 2 diabetes mellitus(T2DM)strengthens insulin resistance(IR)and metabolic abnormalities and significantly increases the risk of heart disease,cancer,and other diseases,and it is characterized by IR and malnutrition.As a metabolic regulation center,adenosine phosphate activated protein kinase(AMPK)mainly responds to the changes in intracellular serine/threonine kinase adenosine monophosphate(AMP)levels.After its activation,AMPK converts the cell metabolism mode from synthesis to decomposition to improve energy metabolism and acts on pathological conditions such as inflammation,ischemia,obesity,and aging.In recent years,a large number of studies have found that AMPK is an important target for the treatment of obesity T2DM.Traditional Chinese medicine(TCM)monomers/extracts and TCM formulas mainly affect the mammalian target of rapamycin(mTOR),recombinant sirtuin 1(SIRT1),nuclear factor erythroid 2-related factor 2(Nrf2),nuclear factor kappa-B(NF-κB),and other key signaling factors by regulating the AMPK signaling pathway,so as to achieve a variety of effects such as regulating metabolism and autophagy,reducing oxidative stress and inflammatory response,and treating obesity T2DM.It also has advantages such as multiple targets,comprehensiveness,and low toxicity.The regulation of the AMPK pathway by TCM in the prevention and treatment of obesity T2DM has become an important research direction at the present and in the future,but there is no systematic summary and induction in this field.Therefore,this article attempts to summarize the composition and regulatory mechanisms of the AMPK signaling pathway in affecting obesity.It provides a review of the current research status of TCM in regulating the AMPK signaling pathway for the prevention and treatment of obesity T2DM,so as to provide a reference for the diagnosis and treatment of obesity T2DM in TCM and the development of new drugs.