Diabetes is one of the common metabolic diseases, mainly divided into two types, type 1 diabetes mellitus and type 2 diabetes mellitus. Insulin resistance is the main performance of type 2 diabetes mellitus which are relative to some gene mutation, genetics, obesity and so on. Protein-tyrosine phosphatase 1B (PTP1B) plays an important role as a negative regulator in insulin signaling pathways that are implicated in metabolic diseases such as obesity and type 2 diabetes. Many evidences from clinical and basical reseach shows that the high expression of PTP1B induces insulin resistance and PTP1B is an effective target for the treatment of type 2 diabetes mellitus. In this review, we briefly introduce composition of PTP1B, and then examine the role of PTP1B in insulin signaling of type 2 diabets mellitus. Finally, we highlight the recent research progress of PTP1B inhibitors used in therapy of type 2 diabetes mellitus. medications such as oxidation, nitrosyaltion, sulfyhydration, sumoylation, phosphorylation and proteolytic cleavage. The diverse modifications illustrated the dynamic regulation of this enzyme and its ability to modulate numerous signaling pathways likely in a cell/tissue-and stimulus-dependent manner, with high specificity and precision. PTP1B, as a potential target for type2 diabetes and obesity, have expanded out of PTP1B gene cDNA span [11]. At the same time, the molecular dynamics studies of interaction between PTP1B and its inhibitors are also going on [12], all which lay a foundation for screening specific PTP1B inhibitors.
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The role of PTP1B in insulin signaling of type 2 diabetes mellitusThe pathogenesis of type 2 diabetes are associated with gene mutation, heredity, obesity and other factors, which main performance is insulin resistance. Dysfunction of pancreatic β cells is one of basic processes and characteristic of the pathogenesis. The increased prevalence of this disease highlights the urgent need to elucidate the underlying molecular mechanisms to aid in therapeutic intervention. Insulin secreted from pancreatic β cells acts as a major regulator of glucose homeostasis through a complex and integrated signaling network. 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 including mitogen-activated protein kinases (MAPK) and PI3K/Akt signal pathways to regulate metabolism. Whereas, when the concentration of insulin is beyond the physiological concentration (hyperinsulinemia), insulin promoted cell proliferation and developments, which may due to the combination of insulin with insulin-like growth factor 1 receptor (IGF-1R) or insulin-...