ArticleAmerican journal of physiology. Endocrinology and metabolism2019
Evidence for a role for Sestrin1 in mediating leucine-induced activation of mTORC1 in skeletal muscle.
Article in American journal of physiology. Endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
- A complementary amino acid formulation enhances exercise-induced skeletal muscle remodeling during resistance training.Physical activity and nutrition · 2026Article
- Impact of Prematurity on Nutrient Signaling and Protein Synthesis in Skeletal Muscle.Annual review of nutrition · 2026Review
- Aerobic exercise improve physical endurance and muscle function by ameliorating oxidative stress and modulating mitochondrial dynamics in aged skeletal muscle.Journal of physiology and biochemistry · 2026Article
- Exercise preconditioning prevents immobilization-induced skeletal muscle atrophy by activating Prmt1-p38/ATF2-Sesn1 signaling axis in C57BL/6J mice.Sports medicine and health science · 2026Article
- Amino Acid Signaling in Skeletal Muscle Is Blunted by Prematurity in a Piglet Model.The Journal of nutrition · 2026Article
- Sestrin2 is Induced Upon Cellular Stress but Has No Effect on Myotube Size or Amino Acid Sensing in C2C12 Myotubes.Biology of the cell · 2025Article
- Analysis of the Stimulative Effect of Arginine on Translation Initiation of Protein Synthesis in Skeletal Muscle.Nutrients · 2025Article
- Accumulation of branched-chain amino acids deteriorates the neuroinflammatory response of Müller cells in diabetic retinopathy via leucine/Sestrin2-mediated sensing of mTOR signaling.Acta diabetologica · 2025Article
- Analysis of the mechanism of skeletal muscle atrophy from the pathway of decreased protein synthesis.Frontiers in physiology · 2025Review
- Amino acids regulating skeletal muscle metabolism: mechanisms of action, physical training dosage recommendations and adverse effects.Nutrition & metabolism · 2024Review
- Tissue-specific expression differences in Ras-related GTP-binding proteins in male rats.Physiological reports · 2024Article
- Sestrin1, 2, and 3 are dispensable for female fertility in mice.Journal of ovarian research · 2024Article
- Article
- Regulation of endothelial ferroptosis by SESN1 in atherosclerosis and its related mechanism.Aging · 2023Article
- Glucose-Induced Activation of mTORC1 is Associated with Hexokinase2 Binding to Sestrins in HEK293T Cells.The Journal of nutrition · 2023Article
- Leucine ingestion promotes mTOR translocation to the periphery and enhances total and peripheral RPS6 phosphorylation in human skeletal muscle.Amino acids · 2023Article
- Alcohol, Resistance Exercise, and mTOR Pathway Signaling: An Evidence-Based Narrative Review.Biomolecules · 2022Review
- Mammalian Target of Rapamycin (mTOR) Signaling at the Crossroad of Muscle Fiber Fate in Sarcopenia.International journal of molecular sciences · 2022Review
- Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health.Advances in nutrition (Bethesda, Md.) · 2022Article
- Convergence of signaling pathways in mediating actions of leucine and IGF-1 on mTORC1 in L6 myoblasts.American journal of physiology. Cell physiology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Previous studies established that leucine stimulates protein synthesis in skeletal muscle to the same extent as a complete mixture of amino acids, and the effect occurs through activation of the mechanistic target of rapamycin in complex 1 (mTORC1). Recent studies using cells in culture showed that the Sestrins bind leucine and are required for leucine-dependent activation of mTORC1. However, the role they play in mediating leucine-dependent activation of the kinase in vivo has been questioned because the dissociation constant of Sestrin2 for leucine is well below circulating and intramuscular levels of the amino acid. The goal of the present study was to compare expression of the Sestrins in skeletal muscle to other tissues and to assess their relative role in mediating activation of mTORC1 by leucine. The results show that the relative expression of the Sestrin proteins varies widely among tissues and that in skeletal muscle Sestrin1 expression is higher than Sestrin3, whereas Sestrin2 expression is markedly lower. Analysis of the dissociation constants of the Sestrins for leucine as assessed by leucine-induced dissociation of the Sestrin·GAP activity toward Rags 2 (GATOR2) complex revealed that Sestrin1 has the highest affinity for leucine and that Sestrin3 has the lowest affinity. In agreement with the dissociation constants calculated using cells in culture, oral leucine administration promotes disassembly of the Sestrin1·GATOR2 complex but not the Sestrin2 or Sestrin3·GATOR2 complex. Overall, the results presented herein are consistent with a model in which leucine-induced activation of mTORC1 in skeletal muscle in vivo occurs primarily through release of Sestrin1 from GATOR2.
Indexed as
Identifiers
What OpenQuestion holds
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.