Type 2 Diabetes Mellitus and Protein-Tyrosine Phosphatase 1B1

Abstract

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. Keywords: 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-...

Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents

“…PTP1B can also influence other biological processes and is expressed in multiple tissues, including the skeletal muscle, liver, adipose tissue, and brain [50]. PTP1B inhibitors enhance insulin and leptin signaling and could potentially improve insulin resistance, normalizing plasma glucose and insulin levels without inducing hypoglycemia [51]. Recently, various PTP1B inhibitors have been developed as drug candidates for T2DM therapy (Figure 11) [8,48,51].…”

“…PTP1B inhibitors enhance insulin and leptin signaling and could potentially improve insulin resistance, normalizing plasma glucose and insulin levels without inducing hypoglycemia [51]. Recently, various PTP1B inhibitors have been developed as drug candidates for T2DM therapy (Figure 11) [8,48,51]. These compounds belong to various types of organic or inorganic compounds: aromatics, nitrogen-containing heterocycles, sulfamides, semi-synthetic terpenes, oligonucleotides, ureas, and vanadium complexes [48,52].…”

Assessing the multitargeted antidiabetic potential of three pomegranate peel‐specific metabolites: An in silico and pharmacokinetics study

“…PTP1β is an integral membrane receptor and acts as a negative insulin-signaling pathway regulator by hydrolyzing the phosphor-tyrosine on the insulin receptor. Inhibition of protein tyrosine phosphatase 1β (PTP1β) restores normal blood glucose levels (Sun et al, 2016;Zhang & Zhang, 2007).…”

“…PTP1β is an integral membrane receptor and acts as a negative insulin‐signaling pathway regulator by hydrolyzing the phosphor‐tyrosine on the insulin receptor. Inhibition of protein tyrosine phosphatase 1β (PTP1β) restores normal blood glucose levels (Sun et al, 2016 ; Zhang & Zhang, 2007 ). Previous research has indicated that increased levels of circulating retinol binding protein‐4 (RBP4) are associated with insulin resistance, metabolic syndrome, impaired glucose tolerance, and T2DM (Kwanbunjan et al, 2018 ; Li et al, 2018 ; Pandey et al, 2015 ; Sun et al, 2014 ).…”

Effect of 8-Week Interval Training on Protein Tyrosine Phosphatase 1B Expression in Gastrocnemius Muscle and Insulin Resistance in Rats with Type 2 Diabetes

“…The use of its antagonists has been considered a means of controlling and treating T2D. This 435 amino acid protein with a molecular weight of 50 kDa is encoded by protein tyrosine phosphatase non-receptor type 1 (PTPN1) (6). In fact, PTP1B interacts with insulin receptors and insulin receptor substrate-1 (IRS-1) and leads to the impairment of glucose uptake by affecting insulin signaling pathways (4).…”