Department of Clinical Biochemistry, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
J Physiol Biochem. 2022 May;78(2):307-322. doi: 10.1007/s13105-021-00860-7. Epub 2022 Jan 6.
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.
胰岛素抵抗是 2 型糖尿病（T2DM）的最重要特征，主要由胰岛素受体（IR）信号转导通路的损伤引起。蛋白酪氨酸磷酸酶 1B（PTP1B）是 IR 信号通路的主要负调控因子之一，广泛表达于各种细胞和组织中。PTP1B 降低了 IR 的磷酸化水平，导致各种组织的胰岛素抵抗。PTP1B 在调节代谢途径中的生理作用的证据来自于全身敲除 PTP1B 的小鼠。全身和组织特异性 PTP1B 敲除小鼠表现出肥胖、胰岛素抵抗和葡萄糖耐量改善。此外，在 PTP1B 缺陷/过表达的小鼠模型中进一步研究了 PTP1B 在 T2DM 及其并发症发病机制中的关键作用。近年来，使用 PTP1B 抑制剂靶向 PTP1B 被认为是治疗 T2DM 的一个有吸引力的靶点。PTP1B 抑制剂可提高胰岛素受体的敏感性，并有能力治疗与胰岛素抵抗相关的疾病。本文总结了 PTP1B 在体内和体外不同组织中的生物学功能。我们还描述了强效 PTP1B 抑制剂作为药物治疗 T2DM 的有效性。
