Review on Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors for the Treatment of Diabetes

Abstract

diabetes is a group of metabolic disease in which person having a high level of blood sugar (blood glucose) or insulin production is improper or person body cell is not properly respond to blood or insulin for a large period. Diabetes is also characterized by hyperglycemia due to insulin improper production. Diabetes is also caused due to pancreas improper insulin production. PTP1B is key regulator of insulin signaling and its use for the treatment of type 2 diabetes and obesity. Insulin secreted from pancreatic β cells acts as a major regulator of glucose homeostasis. Insulin receptor is a kind of transmembrane glycoprotein complex molecules, consisting of two alpha and beta subunits by three disulfide bond connection, among which the alpha subunits locate in the lateral of the cell and beta subunits are across the cell membrane. Insulin binding alpha subunits of the receptor induced phosphorylation of tyrosine residues and protein tyrosine kinase (PTK) of beta subunits, and resulted in a series of phosphorylation and dephosphorylation cascade reactions.PTP1B could catalyze insulin receptor (IR) and insulin receptor substrates (IRS) de phosphorylation, coordinated the balance between phosphorylation and de phosphorylation of tyrosine residues which resulted in insulin signal transduction. PTP1B could de phosphorylate activated JAK2 and STAT3, and prevented leptin signal transduction. There are several PTP1B inhibitors developed by the researchers for the treatment of diabetes mellitus.