ArticleThe Journal of biological chemistry2018
Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Autophagic Pathway on GABARAP Involved in GABANeurochemical research · 2026Review
- HVEM costimulatory domain boosts CAR T cell efficacy against solid tumors via enhanced TRAF-mediated TNF signaling.Cell communication and signaling : CCS · 2026Article
- Fyn Kinase: A Potential Target in Glucolipid Metabolism and Diabetes Mellitus.Current issues in molecular biology · 2025Review
- Has_circ_ASH1L acts as a sponge for miR-1254 to promote the malignant progression of cervical cancer by targeting CD36.Cancer gene therapy · 2025Article
- Impaired suppression of fatty acid release by insulin is a strong predictor of reduced whole-body insulin-mediated glucose uptake and skeletal muscle insulin receptor activation.Acta physiologica (Oxford, England) · 2025Article
- Do SalivaryCurrent issues in molecular biology · 2024Article
- Prognosis significance and potential association between ALDOA and AKT expression in colorectal cancer.Scientific reports · 2024Article
- Ubiquitin-specific protease 11-mediated CD36 deubiquitination acts on C1q/TNF-related protein 9 against atherosclerosis.ESC heart failure · 2023Article
- Fatty Acid Transport and Signaling: Mechanisms and Physiological Implications.Annual review of physiology · 2023Review
- CD36 regulates substrates utilisation in brown adipose tissue of spontaneously hypertensive rats: In vitro study.PloS one · 2023Article
- RING-finger E3 ligases regulatory network in PI3K/AKT-mediated glucose metabolism.Cell death discovery · 2022Review
- [CD36 gene deletion reduces muscle insulin sensitivity in mice by up-regulating PTP1B expression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- The role of CD36 in cardiovascular disease.Cardiovascular research · 2022Review
- Role of UPP pathway in amelioration of diabetes-associated complications.Environmental science and pollution research international · 2021Review
- Article
- The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer.Oncogenesis · 2020Review
- Deubiquitination of CD36 by UCHL1 promotes foam cell formation.Cell death & disease · 2020Article
- Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma.Oncotarget · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Both the magnitude and duration of insulin signaling are important in executing its cellular functions. Insulin-induced degradation of insulin receptor substrate 1 (IRS1) represents a key negative feedback loop that restricts insulin signaling. Moreover, high concentrations of fatty acids (FAs) and glucose involved in the etiology of obesity-associated insulin resistance also contribute to the regulation of IRS1 degradation. The scavenger receptor CD36 binds many lipid ligands, and its contribution to insulin resistance has been extensively studied, but the exact regulation of insulin sensitivity by CD36 is highly controversial. Herein, we found that CD36 knockdown in C2C12 myotubes accelerated insulin-stimulated Akt activation, but the activated signaling was sustained for a much shorter period of time as compared with WT cells, leading to exacerbated insulin-induced insulin resistance. This was likely due to enhanced insulin-induced IRS1 degradation after CD36 knockdown. Overexpression of WT CD36, but not a ubiquitination-defective CD36 mutant, delayed IRS1 degradation. We also found that CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with cullin 7, a key component of the multisubunit cullin-RING E3 ubiquitin ligase complex. Moreover, dissociation of the Src family kinase Fyn from CD36 by free FAs or Fyn knockdown/inhibition accelerated insulin-induced IRS1 degradation, likely due to disrupted IRS1 interaction with CD36 and thus enhanced binding to cullin 7. In summary, we identified a CD36-dependent FA-sensing pathway that plays an important role in negative feedback regulation of insulin activation and may open up strategies for preventing or managing type 2 diabetes mellitus.
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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.