ArticleDiabetes2010
Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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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
67 citing papers in PubMed, 110 citations in OpenAlex.
- Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.Diabetologia · 2022Trial
- Adipose tissue ceramides: emerging lipid components of extracellular vesicles and their influence on metabolic dysregulation.Frontiers in endocrinology · 2026Review
- Ceramide as a Biomarker for HFpEF in Women: Menopause, Aging, and Pregnancy.International journal of molecular sciences · 2025Review
- Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides.Nutrients · 2025Review
- A Gallbladder-Specific Hydrophobic Bile Acid-FXR-MUC1 Signaling Axis Mediates Cholesterol Gallstone Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ceramide microdomains: the major influencers of the sphingolipid media platform.Biochemical Society transactions · 2024Review
- Palmitic Acid Induces Posttranslational Modifications of Tau Protein in Alzheimer's Disease-Related Epitopes and Increases Intraneuronal Tau Levels.Molecular neurobiology · 2024Article
- Anti-Obesity Activity ofNutrients · 2024Article
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Endoplasmic Reticulum Stress and Obesity.Advances in experimental medicine and biology · 2024Review
- Hepatic lipid-associated macrophages mediate the beneficial effects of bariatric surgery against MASH.Research square · 2023Article
- Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants' Cellular Effects.Molecules (Basel, Switzerland) · 2023Review
- Circulating Sphingolipids and Glucose Homeostasis: An Update.International journal of molecular sciences · 2023Review
- Integrative Analysis of Blood Transcriptomics and Metabolomics Reveals Molecular Regulation of Backfat Thickness in Qinchuan Cattle.Animals : an open access journal from MDPI · 2023Article
- Evidence-Based Anti-Diabetic Properties of Plant from the Occitan Valleys of the Piedmont Alps.Pharmaceutics · 2022Review
- Targeting Ceramides and Adiponectin Receptors in the Islet of Langerhans for Treating Diabetes.Molecules (Basel, Switzerland) · 2022Review
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Anti-diabetic potential of Urtica Dioica: current knowledge and future direction.Journal of diabetes and metabolic disorders · 2022Review
- Cordyceps inhibits ceramide biosynthesis and improves insulin resistance and hepatic steatosis.Scientific reports · 2022Article
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveCeramide is now recognized as a negative regulator of insulin signaling by impairing protein kinase B (PKB)/Akt activation. In different cells, two distinct mechanisms have been proposed to mediate ceramide inhibition of PKB/Akt: one involving atypical protein kinase C zeta (PKCzeta) and the other the protein phosphatase-2 (PP2A). We hypothesized that ceramide action through PKCzeta or PP2A might depend on plasma membrane (PM) structural organization and especially on caveolin-enriched domain (CEM) abundance. RESEARCH DESIGN AND
methodsWe have used different PKCzeta mutant constructs or the PP2A inhibitor, okadaic acid (OKA), to selectively inhibit PKCzeta- and PP2A-dependent pathways in cells expressing different caveolin-1 levels and evaluated the impact of insulin and ceramide on PKB/Akt activity in different PM subdomains.
resultsAlthough the PKCzeta-mediated negative effect of ceramide on insulin-stimulated PKB/Akt was dominant in adipocytes, a ceramide action through PP2A outside CEMs, prevented by OKA, was also unraveled. To test the importance of CEM to direct ceramide action through the PKCzeta pathway, we treated 3T3-L1 preadipocytes devoid of CEMs with ceramide and we saw a shift of the lipid-negative action on PKB/Akt to a PP2A-mediated mechanism. In fibroblasts with low CEM abundance, the ceramide-activated PP2A pathway dominated, but could be shifted to a ceramide-activated PKCzeta pathway after caveolin-1 overexpression.
conclusionsOur results show that ceramide can switch from a PKCzeta-dependent mechanism to a PP2A pathway, acting negatively on PKB/Akt, and hence revealing a critical role of CEMs of the PM in this process.
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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.