ArticleScientific reports2015
Protein phosphatase 4 (PP4) functions as a critical regulator in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 30 citations in OpenAlex.
- Biochemical-Cellular crosstalk in diabetes: exploring pathways driving microvascular complications.Molecular biology reports · 2026Review
- SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.American journal of physiology. Endocrinology and metabolism · 2024Article
- LncRNA MEG3 Restrains Hepatic Lipogenesis via the FOXO1 Signaling Pathway in HepG2 Cells.Cell biochemistry and biophysics · 2024Article
- Flavin-Containing Monooxygenase 3 (FMO3) Is Critical for Dioxin-Induced Reorganization of the Gut Microbiome and Host Insulin Sensitivity.Metabolites · 2022Article
- Association between new markers of cardiovascular risk and hepatic insulin resistance in those at high risk of developing type 2 diabetes.Endocrine · 2022Observational
- Action mechanism of hypoglycemic principle 9-(R)-HODE isolated from cortex lycii based on a metabolomics approach.Frontiers in pharmacology · 2022Article
- Protein phosphatase 4 controls circadian clock dynamics by modulating CLOCK/BMAL1 activity.Genes & development · 2021Article
- Diagnostic significance of serum PP4R1 and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus.Diabetology & metabolic syndrome · 2021Article
- Phosphatases in toll-like receptors signaling: the unfairly-forgotten.Cell communication and signaling : CCS · 2021Review
- Protein Phosphatase 4 Promotes Hepatocyte Lipoapoptosis by Regulating RAC1/MLK3/JNK Pathway.Oxidative medicine and cellular longevity · 2021Article
- Effects of Resistant Starch Interventions on Metabolic Biomarkers in Pre-Diabetes and Diabetes Adults.Frontiers in nutrition · 2021Review
- Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe.BMB reports · 2020Review
- Low utilization of glucose in the liver causes diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats.PloS one · 2020Article
- Identification of Protein Phosphatase 4 Inhibitory Protein That Plays an Indispensable Role in DNA Damage Response.Molecules and cells · 2019Article
- Therapeutic Mechanisms of Herbal Medicines Against Insulin Resistance: A Review.Frontiers in pharmacology · 2019Review
- MicroRNA-191, acting via the IRS-1/Akt signaling pathway, is involved in the hepatic insulin resistance induced by cigarette smoke extract.Environmental science and pollution research international · 2018Article
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11 authors at 3 institutions in 1 country.
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Abstract
Protein phosphatase 4 (PP4) was shown to participate in multiple cellular processes, including DNA damage response, cell cycle and embryo development. Recent studies demonstrated a looming role of PP4 in glucose metabolism. However, whether PP4 is involved in hepatic insulin resistance remains poorly understood. The objective of this study was to estimate the role of PP4 in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance. db/db mice and TNF-α-treated C57BL/6J mice were used as hepatic insulin resistance animal models. In vitro models were established in both HepG2 cells and primary hepatocytes by TNF-α treatment. We found that increased expression and activity of PP4 occurred in the livers of db/db mice and TNF-α-induced hepatic insulin resistance both in vitro and in vivo. Actually, PP4 silencing and suppression of PP4 activity ameliorated TNF-α-induced hepatic insulin resistance, whereas over-expression of PP4 caused insulin resistance. We then further investigated the prodiabetic mechanism of PP4 in TNF-α-induced insulin resistance. We found that PP4 formed a complex with IRS-1 to promote phosphorylation of IRS-1 on serine 307 via JNK activation and reduce the expression of IRS-1. Thus, PP4 is an important regulator in inflammatory related insulin resistance.
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