ArticlePloS one2014
Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models: a mechanistic insight.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Pooled it
- Effects of culture media glucose concentration on LHCN-M2 skeletal muscle cell viability, differentiation and metabolic phenotype: a proof-of-concept study.Journal of muscle research and cell motility · 2026Article
- Plasma ceramide Cer24:0 and insulin resistance: associations with TyG and TG/HDL-C in a multicenter study of coronary artery disease cohorts.Frontiers in endocrinology · 2026Observational
- Preclinical research in obesity-associated metabolic diseases using in vitro, multicellular, and non-mammalian models.Journal of physiology and biochemistry · 2025Review
- Intelligent predictive risk assessment and management of sarcopenia in chronic disease patients using machine learning and a web-based tool.European journal of medical research · 2025Article
- Adipose tissue dysfunction disrupts metabolic homeostasis: mechanisms linking fat dysregulation to disease.Frontiers in endocrinology · 2025Review
- Palmitic Acid Induces Posttranslational Modifications of Tau Protein in Alzheimer's Disease-Related Epitopes and Increases Intraneuronal Tau Levels.Molecular neurobiology · 2024Article
- Article
- Experimental cell models of insulin resistance: overview and appraisal.Frontiers in endocrinology · 2024Review
- shRNA-mediated down-regulation of Acsl1 reverses skeletal muscle insulin resistance in obese C57BL6/J mice.PloS one · 2024Article
- Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications.International journal of molecular sciences · 2023Review
- Circulating Sphingolipids and Glucose Homeostasis: An Update.International journal of molecular sciences · 2023Review
- Accumulation of polyunsaturated fatty acid-derived metabolites in the sarcopenic muscle of aging mice.Geriatrics & gerontology international · 2023Article
- The dose-response effects of arachidonic acid on primary human skeletal myoblasts and myotubes.Journal of the International Society of Sports Nutrition · 2023Article
- CerS1 but Not CerS5 Gene Silencing, Improves Insulin Sensitivity and Glucose Uptake in Skeletal Muscle.Cells · 2022Article
- Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway.Frontiers in pharmacology · 2022Article
- Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models.International journal of molecular sciences · 2021Review
- Communications between Mitochondria and Endoplasmic Reticulum in the Regulation of Metabolic Homeostasis.Cells · 2021Review
- Article
- Review
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ceramides are known to promote insulin resistance in a number of metabolically important tissues including skeletal muscle, the predominant site of insulin-stimulated glucose disposal. Depending on cell type, these lipid intermediates have been shown to inhibit protein kinase B (PKB/Akt), a key mediator of the metabolic actions of insulin, via two distinct pathways: one involving the action of atypical protein kinase C (aPKC) isoforms, and the second dependent on protein phosphatase-2A (PP2A). The main aim of this study was to explore the mechanisms by which ceramide inhibits PKB/Akt in three different skeletal muscle-derived cell culture models; rat L6 myotubes, mouse C2C12 myotubes and primary human skeletal muscle cells. Our findings indicate that the mechanism by which ceramide acts to repress PKB/Akt is related to the myocellular abundance of caveolin-enriched domains (CEM) present at the plasma membrane. Here, we show that ceramide-enriched-CEMs are markedly more abundant in L6 myotubes compared to C2C12 myotubes, consistent with their previously reported role in coordinating aPKC-directed repression of PKB/Akt in L6 muscle cells. In contrast, a PP2A-dependent pathway predominantly mediates ceramide-induced inhibition of PKB/Akt in C2C12 myotubes. In addition, we demonstrate for the first time that ceramide engages an aPKC-dependent pathway to suppress insulin-induced PKB/Akt activation in palmitate-treated cultured human muscle cells as well as in muscle cells from diabetic patients. Collectively, this work identifies key mechanistic differences, which may be linked to variations in plasma membrane composition, underlying the insulin-desensitising effects of ceramide in different skeletal muscle cell models that are extensively used in signal transduction and metabolic studies.
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Registered trials
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.