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探索蛋白酪氨酸磷酸酶(PTP)和 PTP-1B 抑制剂在糖尿病治疗中的应用。

Exploring protein tyrosine phosphatases (PTP) and PTP-1B inhibitors in management of diabetes mellitus.

机构信息

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

出版信息

Biomed Pharmacother. 2022 Sep;153:113405. doi: 10.1016/j.biopha.2022.113405. Epub 2022 Jul 14.

Abstract

Type 2 diabetes mellitus (T2D) is a metabolic disorder that knows no boundaries and is spread across the globe. It is one of the most widely spread metabolic disorder, which has now been described as a 'lifestyle' disease. According to the recent study conducted by International Diabetes Federation, the number of diabetic patients will rise from 463 million to 700 million by the year 2045. Conventional therapies often fail to define clear parameters and did not provide early detection in case of diabetes and pre-diabetes. Due to the limitations associated with these therapies, inclination of research is now focused on developing methods or exploring pathways which can overcome these hurdles. Considering these factors, protein tyrosine phosphatase is considered as a promising molecular level legitimate therapeutic target and is known to negatively regulate leptin and insulin signaling pathways. It has shown to be effective in the management of diabetes mellitus in various in vitro and in vivo studies. Various PTP-1B inhibitors have been studied which had shown promising results in the management of diabetes mellitus and associated complications as well. These inhibitors act by increasing insulin sensitivity by inhibiting PTP-1B mediated insulin pathway. In this article we will review the underlying mechanism of protein tyrosine phosphatase and its inhibitors by various PTP 1-B inhibitors for the management of diabetes mellitus and will further throw some light on the challenges and development of these inhibitors.

摘要

2 型糖尿病(T2D)是一种无国界的代谢紊乱疾病,在全球范围内广泛传播。它是最广泛传播的代谢紊乱疾病之一,现在已被描述为一种“生活方式”疾病。根据国际糖尿病联合会最近的研究,到 2045 年,糖尿病患者的数量将从 4.63 亿增加到 7 亿。常规疗法往往无法定义明确的参数,也无法在糖尿病和糖尿病前期进行早期检测。由于这些疗法存在局限性,研究现在倾向于开发可以克服这些障碍的方法或探索途径。考虑到这些因素,蛋白酪氨酸磷酸酶被认为是一种有前途的分子水平的合法治疗靶点,它被认为可以负调控瘦素和胰岛素信号通路。在各种体外和体内研究中,它已被证明在糖尿病的治疗中是有效的。已经研究了各种 PTP-1B 抑制剂,它们在糖尿病及其相关并发症的治疗中显示出了有希望的结果。这些抑制剂通过抑制 PTP-1B 介导的胰岛素通路来增加胰岛素敏感性。在本文中,我们将回顾蛋白酪氨酸磷酸酶及其抑制剂的潜在机制,以及各种 PTP 1-B 抑制剂在糖尿病管理中的应用,并进一步探讨这些抑制剂的挑战和发展。

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