Protein-tyrosine Phosphatase-1B acts as a negative regulator of insulin signal transduction

1998 ◽  
pp. 101-108 ◽  
Author(s):  
John C.H. Byon ◽  
Anasua B. Kusari ◽  
Jyotirmoy Kusari
Keyword(s):  
Signal Transduction ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Insulin Signal Transduction ◽  
Insulin Signal

scholarly journals Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR−/− mouse model of atherosclerosis

2017 ◽  
Vol 131 (20) ◽  
pp. 2489-2501 ◽  
Author(s):  
Dawn Thompson ◽  
Nicola Morrice ◽  
Louise Grant ◽  
 Samantha Le Sommer ◽  
Emma K. Lees ◽  
...  
Keyword(s):  
Mouse Model ◽  
Atherosclerotic Plaque ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Plaque Formation ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Cvd Risk ◽  
Protein Tyrosine ◽  
Atherosclerotic Plaque Formation

Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with type 1 or type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance, due to impaired insulin receptor (IR) signalling. Here, we demonstrate that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR prevents and reverses atherosclerotic plaque formation in an LDLR−/− mouse model of atherosclerosis. Acute (single dose) or chronic PTP1B inhibitor (trodusquemine) treatment of LDLR−/− mice decreased weight gain and adiposity, improved glucose homeostasis and attenuated atherosclerotic plaque formation. This was accompanied by a reduction in both, circulating total cholesterol and triglycerides, a decrease in aortic monocyte chemoattractant protein-1 (MCP-1) expression levels and hyperphosphorylation of aortic Akt/PKB and AMPKα. Our findings are the first to demonstrate that PTP1B inhibitors could be used in prevention and reversal of atherosclerosis development and reduction in CVD risk.

scholarly journals Protein-tyrosine Phosphatase Shp-1 Is a Negative Regulator of IL-4- and IL-13-dependent Signal Transduction

1998 ◽  
Vol 273 (51) ◽  
pp. 33893-33896 ◽  
Author(s):  
S. Jaharul Haque ◽  
Phyllis Harbor ◽  
Mina Tabrizi ◽  
Taolin Yi ◽  
Bryan R. G. Williams
Keyword(s):  
Signal Transduction ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine ◽  
Dependent Signal

Abstract 321: Protein Tyrosine Phosphatase 1B: a Novel Regulator of Proliferation and Apoptosis in the Development of Pulmonary Arterial Hypertension

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shayan Moazeni ◽  
Gregoire Ruffenach ◽  
Shervin Sarji ◽  
Christine Cunningham ◽  
Mylene Vaillancourt ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Protein Tyrosine Phosphatase ◽  
Vascular Remodeling ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Pulmonary Vascular Remodeling ◽  
Protein Tyrosine ◽  
Pulmonary Arterial

Background: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling that leads to an increase in pulmonary arterial pressure resulting in right ventricle failure and death. PAH is driven by pulmonary artery smooth muscle cell (PASMC) proliferation and resistance to apoptosis. Protein Tyrosine Phosphatase 1B (PTP1B), a negative regulator for platelet-derived growth factor (PDGF) and BCL-2, has recently been implicated in PAH in humans. While PDGF and BCL-2 are increased in PAH patients, the pathway for regulating BCL-2 and PDGF is poorly understood. We aim to investigate if PTP1B has a role in proliferation and resistance to apoptosis in PAH in human PACMCs and in the Sugen/Hypoxia/Normoxia (Su/Hx/Nx) PH rat model. Method: Adult male Sprague-Dawley rats were treated with single intraperitoneal dose of SU5416 (20 mg/kg) and kept in Hx for 3 weeks followed by Nx for 2 weeks. Saline treated rats kept in Nx for 5 weeks served as control (n=4/group). RV catheterization was performed terminally for recording RV systolic pressure (RVSP). RV, LV, and interventricular septum (IVS) were isolated for Fulton index (FI, RV/IVS+LV). We analyzed gene expression in lungs via qPCR. Healthy hPASMCs were incubated with a PTP1B inhibitor (Ethyl-3,4-dephostatin) at IC50=0.58ug/ml for 24hrs under Nx conditions and cells were stained with Ki67 to assess proliferation. Results: Su/Hx/Nx rats had severe PH evidenced by a significantly elevated RVSP compared to control (88.97+/- 13.67 vs 28.47+/- 2.22 mmHg, p<0.05). PH rats also showed severely reduced RV function and increased RV hypertrophy (FI= 0.7+/- 0.063 vs 0.274 +/-0.01, p<0.05). PH lungs exhibited severe pulmonary vascular remodeling with excessive growth of the PASMCs. PTP1B was significantly decreased in PH lungs compared to controls (0.158+/-0.0647 vs 1+/-0.06, P<0.05). BCL-2 expression was significantly increased in PAH compared to control (2.01+/-0.162 vs 1 +/-0.1, P<0.01). Inhibition of PTP1B in cultured hPASMCs increased proliferation by ~2 fold as assessed by Ki67 positive cells (n=3). Conclusion: Severe angioproliferative PH in rats is associated with a downregulation of PTP1B and increased expression of BCL-2 and PASMC proliferation.

scholarly journals Roles of Superoxide Radical Anion in Signal Transduction Mediated by Reversible Regulation of Protein-tyrosine Phosphatase 1B

1999 ◽  
Vol 274 (49) ◽  
pp. 34543-34546 ◽  
Author(s):  
William C. Barrett ◽  
Jon P. DeGnore ◽  
Yen-Fang Keng ◽  
Zhong-Yin Zhang ◽  
Moon B. Yim ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Tyrosine Phosphatase ◽  
Radical Anion ◽  
Superoxide Radical ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Superoxide Radical Anion

scholarly journals Pharmacological Effects of JTT-551, a Novel Protein Tyrosine Phosphatase 1B Inhibitor, in Diet-Induced Obesity Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Makoto Ito ◽  
Sumiaki Fukuda ◽  
Shohei Sakata ◽  
Hisayo Morinaga ◽  
Takeshi Ohta
Keyword(s):  
Insulin Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Single Administration ◽  
Leptin Signaling ◽  
Protein Tyrosine ◽  
Diet Induced Obesity ◽  
Stat3 Phosphorylation

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin signaling as well as insulin signaling. JTT-551 is a new PTP1B inhibitor, which is reported to improve glucose metabolism by enhancement of insulin signaling. We have evaluated an antiobesity effect of JTT-551 using diet-induced obesity (DIO) mice. A single administration of JTT-551 was provided to DIO mice with or without leptin, and DIO mice were given food containing JTT-551 for six weeks. A single administration of JTT-551 with leptin treatment enhanced the food inhibition and the signal transducer and activator of transcription 3 (STAT3) phosphorylation in hypothalamus. Moreover, chronic administration of JTT-551 showed an antiobesity effect and an improvement of glucose and lipid metabolism in DIO mice. JTT-551 shows an antiobesity effect possibly by enhancement of leptin signaling and could be useful in the treatment of type 2 diabetes and obesity.

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