ArticleFrontiers in genetics2012
Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2.
Article in Frontiers in genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 81 citations in OpenAlex.
- Rapamycin Does Not Compromise Exercise-Induced Muscular Adaptations in Female Mice.Aging cell · 2025Article
- Review
- Diabetes and its Silent Partner: A Critical Review of Hyperinsulinemia and its Complications.Current diabetes reviews · 2025Review
- Effect of mTORC Agonism via MHY1485 with and without Rapamycin on C2C12 Myotube Metabolism.International journal of molecular sciences · 2024Article
- mTORC1 in energy expenditure: consequences for obesity.Nature reviews. Endocrinology · 2024Review
- Geroprotector drugs and exercise: friends or foes on healthy longevity?BMC biology · 2023Review
- The Selective LAT1 Inhibitor JPH203 Enhances Mitochondrial Metabolism and Content in Insulin-Sensitive and Insulin-Resistant C2C12 Myotubes.Metabolites · 2023Article
- Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging.Communications biology · 2023Article
- mTOR-inhibitors and post-transplant diabetes mellitus: a link still debated in kidney transplantation.Frontiers in medicine · 2023Review
- Article
- Insulin-induced mTOR signaling and gluconeogenesis in renal proximal tubules: A mini-review of current evidence and therapeutic potential.Frontiers in pharmacology · 2022Review
- Skeletal muscle mitochondrial respiration in a model of age-related osteoarthritis is impaired after dietary rapamycin.Experimental gerontology · 2021Article
- Assessment of tantalum nanoparticle-induced MC3T3-E1 proliferation and underlying mechanisms.Journal of materials science. Materials in medicine · 2021Article
- Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.Molecular neurodegeneration · 2021Review
- Article
- Causal association between mTOR-dependent EIF-4E and EIF-4A circulating protein levels and type 2 diabetes: a Mendelian randomization study.Scientific reports · 2020Article
- Is Rapamycin a Dietary Restriction Mimetic?The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Review
- Zishen Huoxue Recipe Protecting Mitochondrial Function of Hypoxic/Reoxygenated Myocardial Cells through mTORC1 Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Article
- A novel rapamycin analog is highly selective for mTORC1 in vivo.Nature communications · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), improves insulin sensitivity in acute studies in vitro and in vivo by disrupting a negative feedback loop mediated by S6 kinase. We find that rapamycin has a clear biphasic effect on insulin sensitivity in C2C12 myotubes, with enhanced responsiveness during the first hour that declines to almost complete insulin resistance by 24-48 h. We and others have recently observed that chronic rapamycin treatment induces insulin resistance in rodents, at least in part due to disruption of mTORC2, an mTOR-containing complex that is not acutely sensitive to the drug. Chronic rapamycin treatment may also impair insulin action via the inhibition of mTORC1-dependent mitochondrial biogenesis and activity, which could result in a buildup of lipid intermediates that are known to trigger insulin resistance. We confirmed that rapamycin inhibits expression of PGC-1α, a key mitochondrial transcription factor, and acutely reduces respiration rate in myotubes. However, rapamycin did not stimulate phosphorylation of PKCθ, a central mediator of lipid-induced insulin resistance. Instead, we found dramatic disruption of mTORC2, which coincided with the onset of insulin resistance. Selective inhibition of mTORC1 or mTORC2 by shRNA-mediated knockdown of specific components (Raptor and Rictor, respectively) confirmed that mitochondrial effects of rapamycin are mTORC1-dependent, whereas insulin resistance was recapitulated only by knockdown of mTORC2. Thus, mTORC2 disruption, rather than inhibition of mitochondria, causes insulin resistance in rapamycin-treated myotubes, and this system may serve as a useful model to understand the effects of rapamycin on mTOR signaling in vivo.
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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.