ArticleThe Journal of biological chemistry2011
An early response transcription factor, Egr-1, enhances insulin resistance in type 2 diabetes with chronic hyperinsulinism.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 90 citations in OpenAlex.
- Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals.Clinical epigenetics · 2018Trial
- Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity.American journal of physiology. Endocrinology and metabolism · 2013Trial
- Article
- Genetic underpinnings of type-2 diabetes (T2D) with colorectal cancer (CRC): In-silico discovery of common molecular signatures, pathogenetic processes and therapeutic candidates.Journal, genetic engineering & biotechnology · 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
- Transcription factors and candidate functional SNPs associated with variation in fatty acid composition from skeletal muscle of pigs.Animal genetics · 2025Article
- Thyrotropin exacerbates insulin resistance by triggering macrophage inflammation in subclinical hypothyroidism.Experimental & molecular medicine · 2025Article
- Identification of EGR1 as a Key Diagnostic Biomarker in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Through Machine Learning and Immune Analysis.Journal of inflammation research · 2025Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target.Clinical and translational medicine · 2023Review
- Genetic Modulation of the GLUT1 Transporter Expression-Potential Relevance in Complex Diseases.Biology · 2022Article
- iPSCs derived from insulin resistant offspring of type 2 diabetic patients show increased oxidative stress and lactate secretion.Stem cell research & therapy · 2022Article
- EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway.Computational and mathematical methods in medicine · 2022Article
- Egr1 plays a major role in the transcriptional response of white adipocytes to insulin and environmental cues.Frontiers in cell and developmental biology · 2022Article
- Hepatocyte-SpecificNutrients · 2021Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Egr1 loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue.Scientific reports · 2020Article
- The balance of protein farnesylation and geranylgeranylation during the progression of nonalcoholic fatty liver disease.The Journal of biological chemistry · 2020Review
- Whole egg consumption increases gene expression within the glutathione pathway in the liver of Zucker Diabetic Fatty rats.PloS one · 2020Article
- Loss of EGR-1 uncouples compensatory responses of pancreatic β cells.Theranostics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the most important characteristics of type 2 diabetes is insulin resistance, during which the patients normally experienced hyperinsulinism stress that would alter insulin signal transduction in insulin target tissues. We have previously found that early growth responsive gene-1 (Egr-1), a zinc finger transcription factor, is highly expressed in db/db mice and in the fat tissue of individuals with type 2 diabetes. In this report, we found that chronic exposure to hyperinsulinism caused persistent Erk/MAPK activity in adipocytes and enhanced insulin resistance in an Egr-1-dependent manner. An elevation in Egr-1 augmented Erk1/2 activation via geranylgeranyl diphosphate synthase (GGPPS). Egr-1-promoted GGPPS transcription increased Ras prenylation and caused Erk1/2 activation. The sustained activation of Erk1/2 resulted in the phosphorylation of insulin receptor substrate-1 at Serine 612. Phosphorylation at this site impaired insulin signaling in adipocytes and reduced glucose uptake. The loss of Egr-1 function, knockdown of GGPPS, or inhibition of Erk1/2 activity in insulin-resistant adipocytes restored insulin receptor substrate-1 tyrosine phosphorylation and increased insulin sensitivity. Our results suggest a new mechanism by which the Egr-1/GGPPS/Erk1/2 pathway is responsible for insulin resistance during hyperinsulinism. This pathway provides a new therapeutic target for increasing insulin sensitivity: inhibiting the function of Egr-1.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.