ArticleThe EMBO journal2011
Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 113 citations in OpenAlex.
- Insulin resistance is associated with mammary mitochondrial dysfunction at the onset of human lactation.The Journal of clinical investigation · 2026Article
- The plant hormone, 6-benzylaminopurine, ameliorates obesity in male and female mice while on a high-fat diet.Molecular metabolism · 2026Article
- Loss of Early Growth Response Protein 1 in the Liver Leads to Hepatic Lipid Accumulation Driven by an Imbalance Between Fatty Acid β-Oxidation and Oxidative Phosphorylation.Gastro hep advances · 2026Article
- Advances in Tumor-Derived Exosomal Non-Coding RNAs Regulating M2 Macrophage Polarization: Molecular Mechanisms and Signaling Pathway.Cancer medicine · 2025Review
- MiR-518b Promotes the Tumorigenesis of Hepatocellular Carcinoma by Targeting EGR1 to Regulate PI3K/AKT/mTOR Signaling Pathway.Cell biochemistry and biophysics · 2025Article
- AGDMP1 alleviates insulin resistance by modulating heat shock protein 60-mediated IRS-1/AKT/GLUT4 pathway and adipose inflammation: A potential therapeutic peptide for gestational diabetes mellitus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Aerobic exercise attenuates high-fat diet-induced glycometabolism impairments in skeletal muscle of rat: role of EGR-1/PTP1B signaling pathway.Nutrition & metabolism · 2024Article
- Adipose tissue-derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity.Clinical and translational medicine · 2024Article
- Short-Term Statin Therapy Induces Hepatic Insulin Resistance Through HNF4α/PAQR9/PPM1α Axis Regulated AKT Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inflammation and immunological disarrays are associated with acute exercise in type 2 diabetes.Journal of diabetes and metabolic disorders · 2024Article
- EGR1/Cancer biology & therapy · 2023Article
- Neuropilin 1 (NRP1) Positively Regulates Adipogenic Differentiation in C3H10T1/2 Cells.International journal of molecular sciences · 2023Article
- The rhythmic coupling of Egr-1 and Cidea regulates age-related metabolic dysfunction in the liver of male mice.Nature communications · 2023Article
- Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target.Clinical and translational medicine · 2023Review
- Insulin increases sensory nerve density and reflex bronchoconstriction in obese mice.JCI insight · 2022Article
- iPSCs derived from insulin resistant offspring of type 2 diabetic patients show increased oxidative stress and lactate secretion.Stem cell research & therapy · 2022Article
- Identification and functional prediction of long noncoding RNAs related to intramuscular fat content in Laiwu pigs.Animal bioscience · 2022Article
- Macrophage-derived secretome is sufficient to confer olanzapine-mediated insulin resistance in human adipocytes.Comprehensive psychoneuroendocrinology · 2021Article
- Review
- Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution.International journal of molecular sciences · 2020Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. But, it is unclear exactly how the two pathways coordinate to regulate insulin sensitivity upon hyperinsulinism stress of type 2 diabetes mellitus (T2DM). Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation.
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