ArticleNature metabolism2021
Liver alanine catabolism promotes skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71 citing papers in PubMed, 126 citations in OpenAlex.
- Vascularized Liver-on-a-Microsphere Reveals Alanine-Glucose Metabolism-Driven Regulation of Liver Function and Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Amino acid-based biological age clock and its implications for human health and aging.Nature communications · 2026Article
- The expanding landscape of the glucagon signaling network: mechanisms and outcomes.Endocrinology · 2026Review
- Female resistance to the metabolic benefits of protein restriction is reversed by ovariectomy in mice.bioRxiv : the preprint server for biology · 2026Article
- Arsenic Exposure Alters Liver Metabolism and Accelerates Skeletal Muscle Atrophy in Female BALB/c Mice.Biological trace element research · 2026Article
- Article
- Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans.Cell reports. Medicine · 2026Article
- Preventive and Ameliorative Effects of Alanine Supplementation on High-Fat Diet-Induced Obesity and Metabolic Dysfunction via the Gut-Liver-Adipose Axis in C57BL/6J Mice.Foods (Basel, Switzerland) · 2026Article
- Development and validation of a predictive model for sarcopenia in patients with type 2 diabetes based on the synergistic mechanism of insulin resistance and inflammation.Frontiers in physiology · 2026Article
- Traditional Chinese Medicine for Diabetic Sarcopenia: A Review and Its Related Mechanisms.Journal of diabetes research · 2026Review
- Diagnostic Model for Obesity and Type 2 Diabetes Mellitus Based on Feature Selection from Fatty Acids, Amino Acids, and Clinical Characteristics.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Impaired cAMP-PKA-CREB1 signalling drives mitochondrial dysfunction in skeletal muscle during cancer cachexia.Nature metabolism · 2025Article
- Mechanical Stimulation Induces Yap Mediated OCTN2 Transcription to Enhance Carnitine Metabolism in Sarcopenia.Journal of cachexia, sarcopenia and muscle · 2025Article
- Unveiling biomarkers via plasma metabolome profiling for diabetic macrovascular and microvascular complications.Cardiovascular diabetology · 2025Article
- Serum metabolomic characteristics and their predictive value for ninety-day prognosis in patients with acute-on-chronic liver failure.World journal of gastroenterology · 2025Observational
- A Multiomic Network Approach to Uncover Disease Modifying Mechanisms of Inborn Errors of Metabolism.Journal of inherited metabolic disease · 2025Article
- Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk.Diabetes · 2025Article
- Exercise Attenuates Skeletal Muscle Atrophy in Senescent SAMP8 Mice: Metabolic Insights from NMR-Based Metabolomics.Molecules (Basel, Switzerland) · 2025Article
- Functions and Therapeutic Potentials of Long Noncoding RNA in Skeletal Muscle Atrophy and Dystrophy.Journal of cachexia, sarcopenia and muscle · 2025Review
- Multi-tissue metabolomics reveal mtDNA- and diet-specific metabolite profiles in a mouse model of cardiometabolic disease.Redox biology · 2025Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both obesity and sarcopenia are frequently associated in ageing, and together may promote the progression of related conditions such as diabetes and frailty. However, little is known about the pathophysiological mechanisms underpinning this association. Here we show that systemic alanine metabolism is linked to glycaemic control. We find that expression of alanine aminotransferases is increased in the liver in mice with obesity and diabetes, as well as in humans with type 2 diabetes. Hepatocyte-selective silencing of both alanine aminotransferase enzymes in mice with obesity and diabetes retards hyperglycaemia and reverses skeletal muscle atrophy through restoration of skeletal muscle protein synthesis. Mechanistically, liver alanine catabolism driven by chronic glucocorticoid and glucagon signalling promotes hyperglycaemia and skeletal muscle wasting. We further provide evidence for amino acid-induced metabolic cross-talk between the liver and skeletal muscle in ex vivo experiments. Taken together, we reveal a metabolic inter-tissue cross-talk that links skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.
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