ArticleThe Journal of clinical investigation2011
Increased SRF transcriptional activity in human and mouse skeletal muscle is a signature of insulin resistance.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Interactome-transcriptome analysis discovers signatures complementary to GWAS Loci of Type 2 Diabetes.Scientific reports · 2016Pooled it
- Multi-omics analysis identifies SMPD1 as a key contributor in sphingolipid pathway for Type 2 diabetes pathogenesis.Genes & genomics · 2026Article
- The Role of Gene Therapy and RNA-Based Therapeutic Strategies in Diabetes.International journal of molecular sciences · 2025Review
- The role of MICAL2 in cancer progression: mechanisms, challenges, and therapeutic potential.Human cell · 2025Review
- Unveiling the link between arsenic toxicity and diabetes: an in silico exploration into the role of transcription factors.Toxicological research · 2024Article
- Fibroblast senescence-associated extracellular matrix promotes heterogeneous lung niche.APL bioengineering · 2024Article
- Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α.Diabetologia · 2024Article
- Common and ethnic-specific derangements in skeletal muscle transcriptome associated with obesity.International journal of obesity (2005) · 2024Article
- Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity.American journal of physiology. Endocrinology and metabolism · 2023Article
- Aberrations in Energetic Metabolism and Stress-Related Pathways Contribute to Pathophysiology in the Neb Conditional Knockout Mouse Model of Nemaline Myopathy.The American journal of pathology · 2023Article
- Blood-based genome-wide DNA methylation correlations across body-fat- and adiposity-related biochemical traits.American journal of human genetics · 2023Article
- Myofiber Baf60c controls muscle regeneration by modulating Dkk3-mediated paracrine signaling.The Journal of experimental medicine · 2023Article
- Zinc finger transcription factor Egf1 promotes non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2023Article
- A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle.The Journal of physiology · 2023Article
- Article
- Rho/SRF Inhibitor Modulates Mitochondrial Functions.International journal of molecular sciences · 2022Article
- Neuregulin (NRG-1β) Is Pro-Myogenic and Anti-Cachectic in Respiratory Muscles of Post-Myocardial Infarcted Swine.Biology · 2022Article
- Downregulation of ALDH6A1 is a New Marker of Muscle Insulin Resistance in Type 2 Diabetes Mellitus.International journal of general medicine · 2022Article
- ΔFBA-Predicting metabolic flux alterations using genome-scale metabolic models and differential transcriptomic data.PLoS computational biology · 2021Article
- Factor Xa Inhibition with Apixaban Does Not Influence Cardiac Remodelling in Rats with Heart Failure After Myocardial Infarction.Cardiovascular drugs and therapy · 2021Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human muscle biopsies from patients with T2D; normoglycemic but insulin-resistant subjects with a parental family history (FH(+)) of T2D; and family history-negative control individuals (FH(–)). Actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator megakaryoblastic leukemia 1 (MKL1) had increased expression in T2D and FH(+) groups. Furthermore, striated muscle activator of Rho signaling (STARS), an activator of SRF, was upregulated in T2D and FH(+) and was inversely correlated with insulin sensitivity. Skeletal muscle from insulin-resistant mice recapitulated this gene expression pattern and showed reduced G-actin and increased nuclear localization of MKL1, each of which regulates SRF activity. Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation, whereas reduction of STARS expression increased insulin signaling and glucose uptake. Pharmacological SRF inhibition by CCG-1423 reduced nuclear MKL1 and improved glucose uptake and tolerance in insulin-resistant mice in vivo. Thus, SRF pathway alterations are linked to insulin resistance, may contribute to T2D pathogenesis, and could represent therapeutic targets.
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