ArticleMolecular metabolism2015
Enhanced insulin signaling in density-enhanced phosphatase-1 (DEP-1) knockout mice.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Single-cell RNA sequencing of the spleen reveals differences in Salmonella typhimurium infection mechanisms between different chicken breeds.Poultry science · 2025Article
- PTPRJ is a negative regulator of insulin signaling in neuronal cells, impacting protein biosynthesis, and neurite outgrowth.Journal of neuroendocrinology · 2024Article
- Exposure to per- and polyfluoroalkyl substances and high-throughput proteomics in Hispanic youth.Environment international · 2024Article
- Review
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- A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells.International journal of molecular sciences · 2022Article
- Protein tyrosine phosphatases (PTPs) in diabetes: causes and therapeutic opportunities.Archives of pharmacal research · 2021Review
- Article
- Pulmonary arterial remodelling by deficiency of peroxisome proliferator-activated receptor-γ in murine vascular smooth muscle cells occurs independently of obesity-related pulmonary hypertension.Respiratory research · 2019Article
- Prenatal Betamethasone interferes with immune system development and alters target cells in autoimmune diabetes.Scientific reports · 2019Article
- Antitumor effects of β-elemene via targeting the phosphorylation of insulin receptor.Endocrine-related cancer · 2019Article
- Targeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out?Molecules (Basel, Switzerland) · 2018Review
- PTPRJ Inhibits Leptin Signaling, and Induction of PTPRJ in the Hypothalamus Is a Cause of the Development of Leptin Resistance.Scientific reports · 2017Article
- Modulation of VEGF receptor 2 signaling by protein phosphatases.Pharmacological research · 2017Review
- The epigenetic signature of systemic insulin resistance in obese women.Diabetologia · 2016Article
- Loss of Protein Tyrosine Phosphatase Receptor J Expression Predicts an Aggressive Clinical Course in Patients with Esophageal Squamous Cell Carcinoma.Pathology oncology research : POR · 2016Article
- Inhibition of Src homology 2 domain-containing phosphatase 1 increases insulin sensitivity in high-fat diet-induced insulin-resistant mice.FEBS open bio · 2016Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveInsulin resistance can be triggered by enhanced dephosphorylation of the insulin receptor or downstream components in the insulin signaling cascade through protein tyrosine phosphatases (PTPs). Downregulating density-enhanced phosphatase-1 (DEP-1) resulted in an improved metabolic status in previous analyses. This phenotype was primarily caused by hepatic DEP-1 reduction.
methodsHere we further elucidated the role of DEP-1 in glucose homeostasis by employing a conventional knockout model to explore the specific contribution of DEP-1 in metabolic tissues. Ptprj (-/-) (DEP-1 deficient) and wild-type C57BL/6 mice were fed a low-fat or high-fat diet. Metabolic phenotyping was combined with analyses of phosphorylation patterns of insulin signaling components. Additionally, experiments with skeletal muscle cells and muscle tissue were performed to assess the role of DEP-1 for glucose uptake.
resultsHigh-fat diet fed-Ptprj (-/-) mice displayed enhanced insulin sensitivity and improved glucose tolerance. Furthermore, leptin levels and blood pressure were reduced in Ptprj (-/-) mice. DEP-1 deficiency resulted in increased phosphorylation of components of the insulin signaling cascade in liver, skeletal muscle and adipose tissue after insulin challenge. The beneficial effect on glucose homeostasis in vivo was corroborated by increased glucose uptake in skeletal muscle cells in which DEP-1 was downregulated, and in skeletal muscle of Ptprj (-/-) mice.
conclusionTogether, these data establish DEP-1 as novel negative regulator of insulin signaling.
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