ArticleJournal of the American Society of Nephrology : JASN2008
Inhibition of SNAT2 by metabolic acidosis enhances proteolysis in skeletal muscle.
Article in Journal of the American Society of Nephrology : JASN, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 59 citations in OpenAlex.
- Combined walking exercise and alkali therapy in patients with CKD4-5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression.European journal of applied physiology · 2013Trial
- Nutrient provision increases signalling and protein synthesis in human skeletal muscle after repeated sprints.European journal of applied physiology · 2011Trial
- Transcriptomic suppression of immune and ECM stability in skeletal muscle of patients with chronic kidney disease.PloS one · 2026Article
- Exhaled Breath Biomarkers Reflect the Inflammasome and Lipidome Changes in Ischemic Heart Disease: A Study Using Machine Learning Models and Network Analysis.Journal of lipid and atherosclerosis · 2025Article
- Long-term leucine supplementation increases body weight in goats by controlling appetite and muscle protein synthesis under protein-restricted conditions.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Resting energy expenditure and kidney disease: a narrative review.Frontiers in nutrition · 2025Review
- Low pH up-regulates interleukin-6 mRNA in L6-G8C5 rat skeletal muscle cells independent of pH sensing by SNAT2(SLC38A2) transporters.FASEB bioAdvances · 2022Article
- Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming.Nature communications · 2021Article
- Dexamethasone acutely suppresses the anabolic SNAT2/SLC38A2 amino acid transporter protein in L6-G8C5 rat skeletal muscle cells.FASEB bioAdvances · 2021Article
- The Amino Acids Sensing and Utilization in Response to Dietary Aromatic Amino Acid Supplementation in LPS-Induced Inflammation Piglet Model.Frontiers in nutrition · 2021Article
- A GC-MS/Single-Cell Method to Evaluate Membrane Transporter Substrate Specificity and Signaling.Frontiers in molecular biosciences · 2021Article
- A selectively suppressing amino acid transporter: Sodium-coupled neutral amino acid transporter 2 inhibits cell growth and mammalian target of rapamycin complex 1 pathway in skeletal muscle cells.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2020Article
- Defect of SLC38A3 promotes epithelial-mesenchymal transition and predicts poor prognosis in esophageal squamous cell carcinoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2020Article
- The application of stable-isotope tracers to study human musculoskeletal protein turnover: a tale of bag filling and bag enlargement.The Journal of physiology · 2019Review
- The Regulatory Role of MeAIB in Protein Metabolism and the mTOR Signaling Pathway in Porcine Enterocytes.International journal of molecular sciences · 2018Article
- Metabolic adaptation of skeletal muscle to hyperammonemia drives the beneficial effects of l-leucine in cirrhosis.Journal of hepatology · 2016Article
- Identification of a Disulfide Bridge in Sodium-Coupled Neutral Amino Acid Transporter 2(SNAT2) by Chemical Modification.PloS one · 2016Article
- Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies.Cancer cell · 2015Article
- Article
- Insulin increases mRNA abundance of the amino acid transporter SLC7A5/LAT1 via an mTORC1-dependent mechanism in skeletal muscle cells.Physiological reports · 2014Article
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 3 institutions in 1 country.
Funding
Abstract
Insulin resistance is a major cause of muscle wasting in patients with ESRD. Uremic metabolic acidosis impairs insulin signaling, which normally suppresses proteolysis. The low pH may inhibit the SNAT2 l-Glutamine (L-Gln) transporter, which controls protein synthesis via amino acid-dependent insulin signaling through mammalian target of rapamycin (mTOR). Whether SNAT2 also regulates signaling to pathways that control proteolysis is unknown. In this study, inhibition of SNAT2 with the selective competitive substrate methylaminoisobutyrate or metabolic acidosis (pH 7.1) depleted intracellular L-Gln and stimulated proteolysis in cultured L6 myotubes. At pH 7.1, inhibition of the proteasome led to greater depletion of L-Gln, indicating that amino acids liberated by proteolysis sustain L-Gln levels when SNAT2 is inhibited by acidosis. Acidosis shifted the dose-response curve for suppression of proteolysis by insulin to the right, confirming that acid increases proteolysis by inducing insulin resistance. Blocking mTOR or phosphatidylinositol-3-kinase (PI3K) increased proteolysis, indicating that both signaling pathways are involved in its regulation. When both mTOR and PI3K were inhibited, methylaminoisobutyrate or acidosis did not stimulate proteolysis further. Moreover, partial silencing of SNAT2 expression in myotubes and myoblasts with small interfering RNA stimulated proteolysis and impaired insulin signaling through PI3K. In conclusion, SNAT2 not only regulates mTOR but also regulates proteolysis through PI3K and provides a link among acidosis, insulin resistance, and protein wasting in skeletal muscle cells.
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.