ArticleDiabetologia2013
Knockdown of PRAS40 inhibits insulin action via proteasome-mediated degradation of IRS1 in primary human skeletal muscle cells.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Sex-specific phosphoproteome responses to calorie restriction and insulin in skeletal muscle from older rats.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Association study between relative expression levels of eight genes and growth rate in Hungarian common carp (Saudi journal of biological sciences · 2022Article
- Cryo-EM insight into the structure of MTOR complex 1 and its interactions with Rheb and substrates.F1000Research · 2019Review
- The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes.Diabetologia · 2018Article
- Article
- PRAS40 signaling in tumor.Oncotarget · 2017Review
- Pim1 inhibition as a novel therapeutic strategy for Alzheimer's disease.Molecular neurodegeneration · 2016Article
- Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Unacylated ghrelin restores insulin and autophagic signaling in skeletal muscle of diabetic mice.Pflugers Archiv : European journal of physiology · 2015Article
- Effects of a brief high-fat diet and acute exercise on the mTORC1 and IKK/NF-κB pathways in rat skeletal muscle.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2015Article
- Effect of Sfrp5 on cytokine release and insulin action in primary human adipocytes and skeletal muscle cells.PloS one · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe proline-rich Akt substrate of 40 kDa (PRAS40) is a component of the mammalian target of rapamycin complex 1 (mTORC1) and among the most prominent Akt substrates in skeletal muscle. Yet the cellular functions of PRAS40 are incompletely defined. This study assessed the function of PRAS40 in insulin action in primary human skeletal muscle cells (hSkMC).
methodsInsulin action was examined in hSkMC following small interfering RNA-mediated silencing of PRAS40 (also known as AKT1S1) under normal conditions and following chemokine-induced insulin resistance.
resultsPRAS40 knockdown (PRAS40-KD) in hSkMC decreased insulin-mediated phosphorylation of Akt by 50% (p < 0.05) as well as of the Akt substrates glycogen synthase kinase 3 (40%) and tuberous sclerosis complex 2 (32%) (both p < 0.05). Furthermore, insulin-stimulated glucose uptake was reduced by 20% in PRAS40-KD myotubes (p < 0.05). Exposing PRAS40-KD myotubes to chemokines caused no additional deterioration of insulin action. PRAS40-KD further reduced insulin-mediated phosphorylation of the mTORC1-regulated proteins p70S6 kinase (p70S6K) (47%), S6 (43%), and eukaryotic elongation 4E-binding protein 1 (100%), as well as protein levels of growth factor receptor bound protein 10 (35%) (all p < 0.05). The inhibition of insulin action in PRAS40-KD myotubes was associated with a reduction in IRS1 protein levels (60%) (p < 0.05), and was reversed by pharmacological proteasome inhibition. Accordingly, expression of the genes encoding E3-ligases F-box protein 32 (also known as atrogin-1) and muscle RING-finger protein-1 and activity of the proteasome was elevated in PRAS40-KD myotubes. CONCLUSIONS/
interpretationInhibition of insulin action in PRAS40-KD myotubes was found to associate with IRS1 degradation promoted by increased proteasome activity rather than hyperactivation of the p70S6K-negative-feedback loop. These findings identify PRAS40 as a modulator of insulin action.
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