以PTP1B为靶点的中药对胰岛素干预HepG2细胞调节作用研究进展

Advances in Research on the Effect of Traditional Chinese Medicine Targeting Protein Tyrosine Phosphatases 1B on Insulin-induced Insulin Resistant HepG2 Cells

2型糖尿病(type 2 diabetes mellitus,T2DM)是胰岛素抵抗或胰岛β细胞功能障碍引起的以高血糖为特征的慢性代谢性疾病。胰岛素抵抗作为T2DM病发的关键要素及明显特点,主要作用于肝脏、肌肉、脂肪等外周靶器官、组织,可降低机体对胰岛素的反应敏感性,致使胰岛素无法产生正常生理效应。肝脏作为机体维持血糖稳态的关键器官,在患者餐后血糖浓度明显增加时,在胰岛素作用下肝脏可有效降低血糖。相反,在血糖浓度降低到一定程度时,会增强肝糖原及糖异生的作用,生成葡萄糖运送至血液中,从而维持血糖稳定。分子水平研究表明2型糖尿病的一个发病机制是胰岛素信号通路障碍。蛋白酪氨酸磷酸酶1B(protein tyrosine phosphatases 1B,PTP1B)是胰岛素信号转导过程中的负调节因子,是2型糖尿病的一个治疗靶点。在肝脏发生胰岛素抵抗的情况下,PTPIB表达水平明显增高,可以将胰岛素受体及受体底物去磷酸化,并影响PI3K/Akt胰岛素信号转导下游相关信号因子的表达,有效降低葡萄糖的吸收作用。该文重点概述以PTPIB为靶点的相关中药对胰岛素干预HepG2细胞的调节作用,探讨相关中药对2型糖尿病的作用机制,以期为相关药物细胞水平的作用机制研究提供参考。

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease characterized by high blood sugar caused by insulin resistance or pancreaticβ-cell dysfunction.Insulin resistance,as a key element and obvious feature of T2 DM,mainly involves peripheral target organs and tissues such as liver,muscle,fat,etc.,which will reduce the sensitivity to insulin and cause insulin to fail to produce normal physiological effects.The liver is a key organ for the patient’s body to maintain blood glucose homeostasis.When the patient’s blood concentration increases significantly after a meal,under the action of insulin,the liver can effectively reduce blood sugar through synthetic sugar.On the contrary,when the blood sugar concentration is reduced,the effects of liver glycogen and gluconeogenesis will be enhanced.Glucose is produced and sent to the patients’blood to maintain blood sugar stability.Studies at the molecular level indicate that one of the pathogenesis of type 2 diabetes is insulin signaling pathway disorder.Protein tyrosine phosphatases 1 B(PTP1 B)is a negative regulator in the process of insulin signaling and a therapeutic target for type 2 diabetes.In the case of liver IR,the expression of PTPIB is significantly increased,which can deacidify the insulin receptor and receptor substrate-1,effectively hinder the downward signaling of insulin,and effectively reduce glucose absorption.This article focuses on the regulatory effects of related Chinese medicines targeting PTPIB on insulin intervention in HepG2 cells,and discusses the mechanism of related Chinese medicines on type 2 diabetes,in order to provide references for the research on the mechanism of related drugs at the cellular level.