The Role of Protein Tyrosine Phosphatase 1B (Ptp1b) in the Pathogenesis of Type 2 Diabetes Mellitus and Its Complications Publisher Pubmed



Teimouri M¹ ; Hosseini H² ; Arabsadeghabadi Z³ ; Babaeikhorzoughi R⁴ ; Gorganifiruzjaee S⁵ ; Meshkani R⁴
Source: Journal of Physiology and Biochemistry Published:2022

Abstract

Insulin resistance, the most important characteristic of the type 2 diabetes mellitus (T2DM), is mostly caused by impairment in the insulin receptor (IR) signal transduction pathway. Protein tyrosine phosphatase 1B (PTP1B), one of the main negative regulators of the IR signaling pathway, is broadly expressed in various cells and tissues. PTP1B decreases the phosphorylation of the IR resulting in insulin resistance in various tissues. The evidence for the physiological role of PTP1B in regulation of metabolic pathways came from whole-body PTP1B-knockout mice. Whole-body and tissue-specific PTP1B-knockout mice showed improvement in adiposity, insulin resistance, and glucose tolerance. In addition, the key role of PTP1B in the pathogenesis of T2DM and its complications was further investigated in mice models of PTP1B deficient/overexpression. In recent years, targeting PTP1B using PTP1B inhibitors is being considered an attractive target to treat T2DM. PTP1B inhibitors improve the sensitivity of the insulin receptor and have the ability to cure insulin resistance-related diseases. We herein summarized the biological functions of PTP1B in different tissues in vivo and in vitro. We also describe the effectiveness of potent PTP1B inhibitors as pharmaceutical agents to treat T2DM. © 2021, The Author(s) under exclusive licence to University of Navarra.