ArticleiScience2023
Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- Alteration in adenosine monophosphate deaminase activity and ferric reducing capacity in diabetic renal failure patients.Journal, genetic engineering & biotechnology · 2026Article
- Narrative Review: Sugar and Rice and the Diabetes Epidemic in India-A Historical Context.Nutrients · 2026Review
- Construction and validation of a machine learning model to predict the sarcopenic obesity population.Medicine · 2026Article
- Investigation of the effects and underlying mechanisms of adenylate kinase 1 on inosine monophosphate deposition in Beijing-You chickens.Poultry science · 2026Article
- Sarcopenia in Kidney Transplantation: Bridging Pathophysiology to Patient-Centered Care.Nutrients · 2026Review
- Integrated analysis of the adipocyte plasma membrane proteome reveals KCC1 and PIT2 as novel insulin-responsive transporters.The Journal of biological chemistry · 2026Article
- Predictive model of sarcopenia in chronic kidney disease: an integrated approach of bioinformatics, machine learning, and clinical validation.Frontiers in physiology · 2026Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- The Pathologic Actions of Phosphate in CKD.Kidney360 · 2025Review
- Sarcopenia associated with increased risk of comorbidities among individuals with chronic kidney disease: insights from a prospective cohort.Frontiers in public health · 2025Article
- Activation of AMPD2 drives metabolic dysregulation and liver disease in mice with hereditary fructose intolerance.Communications biology · 2024Article
- Skeletal Muscle Injury in Chronic Kidney Disease-From Histologic Changes to Molecular Mechanisms and to Novel Therapies.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Sarcopenia is a common and devastating condition in patients with chronic kidney disease (CKD). Here, we provide evidence that the kidney-muscle crosstalk in sarcopenia is mediated by reduced insulin sensitivity and the activation of the muscle-specific isoform of AMP deaminase, AMPD1. By using a high protein-based CKD model of sarcopenia in mice and differentiated human myotubes, we show that urea reduces insulin-dependent glucose and phosphate uptake by the skeletal muscle, thus contributing to the hyperphosphatemia observed in CKD whereas depleting intramuscular phosphate needed to restore energy and inhibit AMPD1. Hyperactivated AMPD1, in turn, aggravates the low energy state in the muscle by removing free adenosine monophosphate (AMP) and producing proinflammatory factors and uric acid which contribute to the progression of kidney disease. Our data provide molecular and metabolic evidence supporting the use of strategies aimed to improve insulin sensitivity and to block AMPD1 to prevent sarcopenia in subjects with CKD.
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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.