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PTP1B

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https://www.readbyqxmd.com/read/29769704/effect-of-protocatechuic-acid-on-insulin-responsiveness-and-inflammation-in-visceral-adipose-tissue-from-obese-individuals-possible-role-for-ptp1b
#1
Paulina Ormazabal, Beatrice Scazzocchio, Rosaria Varì, Carmela Santangelo, Massimo D'Archivio, Gianfranco Silecchia, Annunziata Iacovelli, Claudio Giovannini, Roberta Masella
BACKGROUND/OBJECTIVES: The occurrence of chronic inflammation in visceral adipose tissue (VAT) in obese subjects precipitates the development of insulin resistance and type 2 diabetes (T2D). Anthocyanins and their main metabolite protocatechuic acid (PCA) have been demonstrated to stimulate insulin signaling in human adipocytes. The aim of this study was to investigate whether PCA is able to modulate insulin responsiveness and inflammation in VAT from obese (OB) and normal weight (NW) subjects...
May 16, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29751237/current-anti-diabetic-agents-and-their-molecular-targets-a-review
#2
REVIEW
Nagaraju Kerru, Ashona Singh-Pillay, Paul Awolade, Parvesh Singh
Diabetes mellitus is a medical condition characterized by the body's loss of control over blood sugar. The frequency of diagnosed cases and consequential increases in medical costs makes it a rapidly growing chronic disease that threatens human health worldwide. In addition, its unnerving statistical projections are perilous to both the economy of the nation and man's life expectancy. Type-I and type-II diabetes are the two clinical forms of diabetes mellitus. Type-II diabetes mellitus (T2DM) is illustrated by the abnormality of glucose homeostasis in the body, resulting in hyperglycemia...
May 3, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29745030/synthesis-and-biological-evaluation-of-novel-n-aryl-%C3%AF-benzoazol-2-yl-sulfanylalkanamides-as-dual-inhibitors-of-%C3%AE-glucosidase-and-protein-tyrosine-phosphatase-1b
#3
Mei-Yan Wang, Xian-Chao Cheng, Xiu-Bo Chen, Yu Li, Lan-Lan Zang, Yu-Qing Duan, Ming-Zhu Chen, Peng Yu, Hua Sun, Run-Ling Wang
α-Glucosidase is known to catalyze the digestion of carbohydrates and release free glucose into the digestive tract. Protein tyrosine phosphatase 1B (PTP1B) is engaged in the dephosphorylation of the insulin receptor and regulation of insulin sensitivity. Therefore, dual antagonists by targeting both α-glucosidase and PTP1B may be potential candidates for type 2 diabetes therapy. In this work, three series of novel N-aryl-ω-(benzoazol-2-yl)-sulfanylalkanamides were synthesized and assayed for their α-glucosidase and PTP1B inhibitory activities, respectively...
May 9, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29743567/mir-338-3p-functions-as-a-tumor-suppressor-in-gastric-cancer-by-targeting-ptp1b
#4
Feng Sun, Mengchao Yu, Jing Yu, Zhijian Liu, Xinyan Zhou, Yanqing Liu, Xiaolong Ge, Haidong Gao, Mei Li, Xiaohong Jiang, Song Liu, Xi Chen, Wenxian Guan
Gastric cancer (GC) is one of the most common malignant tumors and peritoneal metastasis is the primary cause for advanced GC's mortality. Protein-tyrosine phosphatase 1B (PTP1B) functions as an oncogene and involves in carcinogenesis and cancer dissemination. However, the function and regulation of PTP1B in GC remain poorly understood. In this study, we found that PTP1B was upregulated in GC tissues and overexpression of PTP1B in vitro promoted cell migration and prevented apoptosis. Then, we predicted that PTP1B was a target of miR-338-3p and we revealed an inverse correlation between miR-338-3p levels and PTP1B protein levels in GC tissues...
May 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29742155/the-hsv-1-mechanisms-of-cell-to-cell-spread-and-fusion-are-critically-dependent-on-host-ptp1b
#5
Jillian C Carmichael, Hiroki Yokota, Rebecca C Craven, Anthony Schmitt, John W Wills
All herpesviruses have mechanisms for passing through cell junctions, which exclude neutralizing antibodies and offer a clear path to neighboring, uninfected cells. In the case of herpes simplex virus type 1 (HSV-1), direct cell-to-cell transmission takes place between epithelial cells and sensory neurons, where latency is established. The spreading mechanism is poorly understood, but mutations in four different HSV-1 genes can dysregulate it, causing neighboring cells to fuse to produce syncytia. Because the host proteins involved are largely unknown (other than the virus entry receptor), we were intrigued by an earlier discovery that cells infected with wild-type HSV-1 will form syncytia when treated with salubrinal...
May 9, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29731242/therapeutic-effects-of-the-allosteric-protein-tyrosine-phosphatase-1b-inhibitor-ky-226-on-experimental-diabetes-and-obesity-via-enhancements-in-insulin-and-leptin-signaling-in-mice
#6
Yuma Ito, Masaki Fukui, Mamoru Kanda, Ko Morishita, Yoshimichi Shoji, Tatsuya Kitao, Eiichi Hinoi, Hiroaki Shirahase
The anti-diabetic and anti-obesity effects of the allosteric protein tyrosine phosphatase 1B (PTP1B) inhibitor 4-(biphenyl-4-ylmethylsulfanylmethyl)-N-(hexane-1-sulfonyl)benzoylamide (KY-226) were pharmacologically evaluated. KY-226 inhibited human PTP1B activity (IC50  = 0.28 μM), but did not exhibit peroxisome proliferator-activated receptor γ (PPARγ) agonist activity. In rodent preadipocytes (3T3-L1), KY-226 up to 10 μM had no effects on adipocyte differentiation, whereas pioglitazone, a PPARγ agonist, markedly promoted it...
March 6, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29729863/quadruple-high-resolution-%C3%AE-glucosidase-%C3%AE-amylase-ptp1b-radical-scavenging-profiling-combined-with-high-performance-liquid-chromatography-high-resolution-mass-spectrometry-solid-phase-extraction-nuclear-magnetic-resonance-spectroscopy-for-identification-of
#7
Yong Zhao, Kenneth Thermann Kongstad, Anna Katharina Jäger, John Nielsen, Dan Staerk
In this paper, quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling combined with HPLC-HRMS-SPE-NMR were used for studying the polypharmacological properties of crude root bark extract of Morus alba L. This species is used as an anti-diabetic principle in many traditional treatment systems around the world, and the crude ethyl acetate extract of M. alba root bark was found to inhibit α-glucosidase, α-amylase and protein-tyrosine phosphatase 1B (PTP1B) with IC50 values of 1...
April 21, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29721029/effects-of-modified-sanzi-yangqin-decoction-on-tyrosine-phosphorylation-of-irs-1-in-skeletal-muscle-of-type-2-diabetic-rats
#8
Ya Wang, Xiaojin La, Chunyu Tian, Yushan Dong, Feng Qi, Changlong Qiu, Xiujuan Gao, Ji'an Li
This study aimed to investigate the effect of Modified Sanzi Yangqin Decoction on tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in skeletal muscle of type 2 diabetic rats. The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injections. Diabetic model rats were randomly divided into 5 groups: the model control group, the metformin group, and Modified Sanzi Yangqin Decoction groups of low, medium, and high doses. OGTT was conducted every two weeks during treatment period...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29708510/tumor-secreted-pros1-inhibits-macrophage-m1-polarization-to-reduce-antitumor-immune-response
#9
Eric Ubil, Laura Caskey, Alisha Holtzhausen, Debra Hunter, Charlotte Story, H Shelton Earp
Tyro3, Axl, Mer (TAM) receptor tyrosine kinases reduce inflammatory, innate immune responses. We demonstrate that tumor-secreted protein S (Pros1), a Mer/Tyro3 ligand, decreased macrophage M1 cytokine expression in vitro and in vivo. In contrast, tumor cells with CRISPR-based deletion of Pros1 failed to inhibit M1 polarization. Tumor cell-associated Pros1 action was abrogated in macrophages from Mer- and Tyro3- but not Axl-KO mice. In addition, several other murine and human tumor cell lines suppressed macrophage M1 cytokine expression induced by IFN-γ and LPS...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29705606/neuroprotective-effects-of-protein-tyrosine-phosphatase-1b-inhibitor-on-cerebral-ischemia-reperfusion-in-mice
#10
Meiling Sun, Hisanao Izumi, Yasuharu Shinoda, Kohji Fukunaga
Akt (Protein kinase B, PKB), a serine/threonine kinase, plays a critical role in cell development, growth, and survival. Akt phosphorylation mediates a neuroprotective effect against ischemic injury. Recently, a protein-tyrosine phosphatase-1B (PTP1B) inhibitor (KY-226) was developed to elicit anti-diabetic and anti-obesity effects via enhancement of insulin signaling. Previously, we reported that the nonselective PTP1B inhibitor, sodium orthovanadate, rescued neurons from delayed neuronal death during brain ischemia...
April 26, 2018: Brain Research
https://www.readbyqxmd.com/read/29705509/protection-against-gamma-radiation-injury-by-protein-tyrosine-phosphatase-1b
#11
Marina Mojena, María Pimentel-Santillana, Adrián Povo-Retana, Victoria Fernández-García, Silvia González-Ramos, Patricia Rada, Alberto Tejedor, Daniel Rico, Paloma Martín-Sanz, Angela M Valverde, Lisardo Boscá
Protein tyrosine phosphatase 1B (PTP1B) is widely expressed in mammalian tissues, in particular in immune cells, and plays a pleiotropic role in dephosphorylating many substrates. Moreover, PTP1B expression is enhanced in response to pro-inflammatory stimuli and to different cell stressors. Taking advantage of the use of mice deficient in PTP1B we have investigated the effect of γ-radiation in these animals and found enhanced lethality and decreased respiratory exchange ratio vs. the corresponding wild type animals...
April 21, 2018: Redox Biology
https://www.readbyqxmd.com/read/29701158/molecular-docking-in-silico-admet-study-and-development-of-1-6-dihydropyrimidine-derivative-as-protein-tyrosine-phosphatase-inhibitor-an-approach-to-design-and-develop-antidiabetic-agents
#12
Ashish D Patel, Rahul Barot, Inaxi Parmar, Ishan Panchal, Umang Shah, Mehul Patel, Bharat Mishtry
1,6-Dihydropyrimidine exerts notable pharmacological efficiency and emerged as integral backbones for treatment of type-II diabetes mellitus. To optimize the in vitro and in-silico study we carried out on substituted 1,6-Dihydropyrimidine. The objective of the present study is to evaluate the binding interaction of 1,6-Dihydropyrimidine compounds with protein tyrosine phosphatase (PTP1B) enzyme and also check ADME/T properties of best scored compounds. The in-silico study (docking) was carried out through target protein tyrosine phosphatase (PTP1B) retrieved from protein data bank having PDB ID: 2QBS and the anti diabetic activity of the test compounds was tested against protein tyrosine phosphatase (PTP1B) enzyme by using Calbiochem® PTP1B colorimetric assay kit...
April 26, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29671829/anti-diabetic-effects-of-acankoreagenin-from-the-leaves-of-acanthopanax-gracilistylus-herb-in-rin-m5f-cells-via-suppression-of-nf-%C3%AE%C2%BAb-activation
#13
Man-Xia Lu, Yang Yang, Qin-Peng Zou, Jiao Luo, Bin-Bei Zhang, Xiang-Qian Liu, Eun-Hee Hwang
Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. In this manuscript, acankoreagenin isolated from the leaves of Acanthopanax gracilistylus (LAG) is thought to possess excellent anti-diabetic properties. In vitro, anti-diabetic activities were assessed based on the inhibitory activities with α-glucosidase (IC50 13.01 μM), α-amylase (IC50 30.81 μM), and PTP1B (IC50 16.39 μM). Acankoreagenin showed better anti-diabetic effects...
April 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29665732/3%C3%AE-19-dihydroxyl-ent-pimara-8-14-15-diene-a-new-diterpenoid-from-the-rhizomes-of-ricinus-communis
#14
Sheng-Nan Zhang, Jin Zeng, Ya-Nan Tan, Rui-Jing Ma, Gui-Jie Zhang, Heng-Shan Wang, Qin-Gang Tan
A new natural product, 3α,19-dihydroxyl-ent-pimara-8(14),15-diene (1), which possesses an α-orientation hydroxymethyl at C-4 and ∆8,14 groups, as well as eight known compounds, was isolated from the rhizomes of Ricinus communis. The structure of 1 was elucidated by extensive spectroscopic methods and its absolute configurations were confirmed by X-ray crystallographic analysis. The inhibitory rate of 1 against protein tyrosine phosphatase 1B (PTP1B) was 49.49% at the concentration of 6.58 × 10-5  mol/L...
April 18, 2018: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/29652789/terpenoids-from-the-soft-coral-sinularia-sp-collected-in-yongxing-island
#15
Guo-Fei Qin, Xu-Li Tang, Yan-Ting Sun, Xiang-Chao Luo, Jing Zhang, Leen van Ofwegen, Ping-Jyun Sung, Ping-Lin Li, Guo-Qiang Li
Three new sesquiterpenoids (sinuketal ( 1 ), sinulins A and B ( 2 and 3 )) and two new cembranoids (sinulins C and D ( 4 and 5 )), as well as eight known sesquiterpenoids ( 6–13 ) and eight known cembranoids ( 14–21 ), were isolated from the Xisha soft coral Sinularia sp. Their structures were elucidated by extensive spectroscopic analysis. Compound 1 possesses an unprecedented isopropyl-branched bicyclo [6.3.0] undecane carbon skeleton with unique endoperoxide moiety, and a plausible biosynthetic pathway of it was postulated...
April 13, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29608303/virtual-screening-of-novel-and-selective-inhibitors-of-ptp1b-over-tcptp-using-a-bidentate-inhibition-strategy
#16
Xi Chen, Qiang Gan, Changgen Feng, Xia Liu, Qian Zhang
Protein tyrosine phosphatase 1B (PTP1B), a promising target for II diabetes, obesity and cancer therapeutics, plays an important negative role in insulin signaling pathways. However, the lack of selective over other PTPs, especially for TCPTP, is still a challenge for inhibitors development. Recent studies suggest that the second pTyr binding site, close to the catalytic domain, may elevate binding affinity while bringing selectivity to inhibitors. Inspired by these studies, a virtual screening method based on a bidentate strategy was operated to identify novel selective inhibitors of PTP1B...
April 2, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29605633/peroxiredoxin-2-mediates-insulin-sensitivity-of-skeletal-muscles-through-regulation-of-protein-tyrosine-phosphatase-oxidation
#17
Jung-Hak Kim, Sun-Ji Park, Unbin Chae, Joongbae Seong, Hyun-Shik Lee, Sang-Rae Lee, Seunghoon Lee, Dong-Seok Lee
Insulin signaling is essential for regulating glucose homeostasis. Numerous studies have demonstrated that reactive oxygen species (ROS) affect insulin signaling, and low ROS levels can act as a signal to regulate cellular function. Peroxiredoxins (Prxs) are highly abundant and widely expressed antioxidant enzymes. However, it is unclear whether antioxidant enzymes, such as Prx2, mediate insulin signaling. The aim of our study was to investigate the influence of Prx2 deficiency on insulin signaling. Our western blot results showed that Prx2 deficiency enhanced insulin signaling and increased oxidation of protein tyrosine phosphatase 1B (PTP1B) and phosphatase and tensin homologue (PTEN) in mouse embryonic fibroblasts (MEFs) treated with insulin...
March 29, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29604334/alternative-translation-initiation-of-caveolin-2-desensitizes-insulin-signaling-through-dephosphorylation-of-insulin-receptor-by-ptp1b-and-causes-insulin-resistance
#18
Hayeong Kwon, Jaewoong Lee, Donghwan Jang, Moonjeong Choi, Kyuho Jeong, Yunbae Pak
Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance...
March 28, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29587405/further-new-diterpenoids-as-ptp1b-inhibitors-from-the-xisha-soft-coral-sinularia-polydactyla
#19
Fei Ye, Zheng-Dan Zhu, Yu-Cheng Gu, Jia Li, Wei-Liang Zhu, Yue-Wei Guo
A new prenyleudesmane type diterpene, sinupol ( 8 ), and a new capnosane type diterpenoid, sinulacetate ( 9 ), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes ( 4 - 7 and 10 ). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds ( 8 and 9 ) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity...
March 25, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29570727/mir-126-5p-by-direct-targeting-of-jnk-interacting-protein-2-jip-2-plays-a-key-role-in-theileria-infected-macrophage-virulence
#20
Malak Haidar, Zineb Rchiad, Hifzur Rahman Ansari, Fathia Ben-Rached, Shahin Tajeri, Perle Latre De Late, Gordon Langsley, Arnab Pain
Theileria annulata is an apicomplexan parasite that infects and transforms bovine macrophages that disseminate throughout the animal causing a leukaemia-like disease called tropical theileriosis. Using deep RNAseq of T. annulata-infected B cells and macrophages we identify a set of microRNAs induced by infection, whose expression diminishes upon loss of the hyper-disseminating phenotype of virulent transformed macrophages. We describe how infection-induced upregulation of miR-126-5p ablates JIP-2 expression to release cytosolic JNK to translocate to the nucleus and trans-activate AP-1-driven transcription of mmp9 to promote tumour dissemination...
March 23, 2018: PLoS Pathogens
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