ArticleDiabetologia2013
Inducible liver-specific knockdown of protein tyrosine phosphatase 1B improves glucose and lipid homeostasis in adult mice.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Novel Yunaconitine Derivatives as Protein Tyrosine Phosphatase 1B Inhibitors and Radical Scavenger: Design, Synthesis, in Vitro Cellular Evaluation, and Molecular Docking Study.Chemistry & biodiversity · 2026Article
- Exploring cutting-edge approaches in diabetes care: from nanotechnology to personalized therapeutics.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Protein tyrosine phosphatase 1B in metabolic diseases and drug development.Nature reviews. Endocrinology · 2024Review
- Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.Current drug targets · 2024Review
- CX08005, a Protein Tyrosine Phosphatase 1B Inhibitor, Attenuated Hepatic Lipid Accumulation and Microcirculation Dysfunction Associated with Nonalcoholic Fatty Liver Disease.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Potential Therapeutic Target Protein Tyrosine Phosphatase-1B for Modulation of Insulin Resistance with Polyphenols and Its Quantitative Structure-Activity Relationship.Molecules (Basel, Switzerland) · 2022Article
- Mitochondrial oxidative function in NAFLD: Friend or foe?Molecular metabolism · 2021Review
- Short-Term Strength Exercise Reduces Hepatic Insulin Resistance in Obese Mice by Reducing PTP1B Content, Regardless of Changes in Body Weight.International journal of molecular sciences · 2021Article
- Evaluation of the Hypoglycemic Activity ofFrontiers in pharmacology · 2021Article
- Hepatic protein-tyrosine phosphatase 1B disruption and pharmacological inhibition attenuate ethanol-induced oxidative stress and ameliorate alcoholic liver disease in mice.Redox biology · 2020Article
- CYC31, A Natural Bromophenol PTP1B Inhibitor, Activates Insulin Signaling and Improves Long Chain-Fatty Acid Oxidation in C2C12 Myotubes.Marine drugs · 2020Article
- Article
- Exploration the Mechanism of Doxorubicin-Induced Heart Failure in Rats by Integration of Proteomics and Metabolomics Data.Frontiers in pharmacology · 2020Article
- Drug Delivery System in the Treatment of Diabetes Mellitus.Frontiers in bioengineering and biotechnology · 2020Review
- The Role of Protein Tyrosine Phosphatase (PTP)-1B in Cardiovascular Disease and Its Interplay with Insulin Resistance.Biomolecules · 2019Review
- Endoplasmic Reticulum Stress: A Critical Molecular Driver of Endothelial Dysfunction and Cardiovascular Disturbances Associated with Diabetes.International journal of molecular sciences · 2019Review
- Involvement of PPARγ/FSP27 in the pathogenic mechanism underlying insulin resistance: tipping the balance between lipogenesis and fat storage in adult catch-up growth rats.Nutrition & metabolism · 2019Article
- Crosstalk Between Oxidative Stress and Endoplasmic Reticulum (ER) Stress in Endothelial Dysfunction and Aberrant Angiogenesis Associated With Diabetes: A Focus on the Protective Roles of Heme Oxygenase (HO)-1.Frontiers in physiology · 2019Review
- Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor.British journal of pharmacology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisProtein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signalling. Hepatic PTP1B deficiency, using the Alb-Cre promoter to drive Ptp1b deletion from birth in mice, improves glucose homeostasis, insulin sensitivity and lipid metabolism. The aim of this study was to investigate the therapeutic potential of decreasing liver PTP1B levels in obese and insulin-resistant adult mice.
methodsInducible Ptp1b liver-specific knockout mice were generated using SA-Cre-ER(T2) mice crossed with Ptp1b floxed (Ptp1b(fl/fl)) mice. Mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and insulin resistance. Tamoxifen was administered in the HFD to induce liver-specific deletion of Ptp1b (SA-Ptp1b(-/-) mice). Body weight, glucose homeostasis, lipid homeostasis, serum adipokines, insulin signalling and endoplasmic reticulum (ER) stress were examined.
resultsDespite no significant change in body weight relative to HFD-fed Ptp1b(fl/fl) control mice, HFD-fed SA-Ptp1b(-/-) mice exhibited a reversal of glucose intolerance as determined by improved glucose and pyruvate tolerance tests, decreased fed and fasting blood glucose and insulin levels, lower HOMA of insulin resistance, circulating leptin, serum and liver triacylglycerols, serum NEFA and decreased HFD-induced ER stress. This was associated with decreased glycogen synthase, eukaryotic translation initiation factor-2α kinase 3, eukaryotic initiation factor 2α and c-Jun NH2-terminal kinase 2 phosphorylation, and decreased expression of Pepck. CONCLUSIONS/
interpretationInducible liver-specific PTP1B knockdown reverses glucose intolerance and improves lipid homeostasis in HFD-fed obese and insulin-resistant adult mice. This suggests that knockdown of liver PTP1B in individuals who are already obese/insulin resistant may have relatively rapid, beneficial therapeutic effects.
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Registered trials
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