ArticleThe Journal of clinical investigation2009
Endogenous glucocorticoids and impaired insulin signaling are both required to stimulate muscle wasting under pathophysiological conditions in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03229395 (Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids), which is not on this map. Cited by 105 papers, 2 of them syntheses that pooled it.
What it found
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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.
Alterations of Muscle Secretome Associated With Muscle Atrophy Caused by Glucocorticoids
Who cites it
105 citing papers in PubMed, 2 syntheses or guidelines pooled it, 197 citations in OpenAlex.
- Effects of sodium bicarbonate, cholecalciferol, and protein supplementation interventions on muscle mass and metabolic disturbances in patients with chronic kidney disease: a systematic review and network meta-analysis.Frontiers in nutrition · 2026Pooled it
- Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease: a systematic review and meta-analysis.Journal of cachexia, sarcopenia and muscle · 2023Pooled it
- Targeting nuclear receptors in muscular dystrophies and regenerative myogenesis.Frontiers in cell and developmental biology · 2026Review
- Optineurin binding to the novel interacting partner Junction plakoglobin prevents muscle atrophy in mice.PLoS biology · 2026Article
- Chronic Kidney Disease, Sarcopenia, and Hormonal-Metabolic Alterations: An Intriguing Association.Kidney & blood pressure research · 2026Review
- Negative Impact of p21-Activated Kinase 4-Mediated AMP-Activated Protein Kinase Inhibition on Sarcopenia in Mice and Humans.MedComm · 2025Article
- Frailty compared to sarcopenia as the predictor of mortality for elderly hemodialysis patients.Journal of nephrology · 2025Article
- SIRT2 attenuates stress-induced skeletal muscle atrophy by inhibiting glucocorticoid receptor signalling.bioRxiv : the preprint server for biology · 2025Article
- Protein kinase ROCK1 activates mitochondrial fission linking to oxidative stress and muscle atrophy.Kidney international · 2025Article
- Protein-energy wasting in chronic kidney disease: mechanisms responsible for loss of muscle mass and function.Kidney research and clinical practice · 2025Article
- Targeting Sarcopenia in CKD: The Emerging Role of GLP-1 Receptor Agonists.International journal of molecular sciences · 2025Review
- The longitudinal mediating effect of life-space mobility on the relationship between nutritional status and cognitive function in community-dwelling older stroke patients.Frontiers in public health · 2025Article
- The glucocorticoid receptor acts locally to protect dystrophic muscle and heart during disease.Disease models & mechanisms · 2024Article
- Identification of molecular mediators of renal sarcopenia risk: a mendelian randomization analysis.The journal of nutrition, health & aging · 2024Article
- βFrontiers in physiology · 2024Article
- Clinical features and molecular mechanism of muscle wasting in end stage renal disease.BMB reports · 2023Review
- Nutritional Strategies to Prevent Muscle Loss and Sarcopenia in Chronic Kidney Disease: What Do We Currently Know?Nutrients · 2023Review
- Fibroblast Growth Factor 23 and Muscle Wasting: A Metabolic Point of View.Kidney international reports · 2023Review
- Prevalence and Mechanisms of Skeletal Muscle Atrophy in Metabolic Conditions.International journal of molecular sciences · 2023Review
- A clinical herbal prescription Gu-Shu-Kang capsule exerted beneficial effects on the musculoskeletal system of dexamethasone-treated mice by acting on tissue IGF-1 signalling pathway.Pharmaceutical biology · 2022Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Muscle wasting is associated with a number of pathophysiologic conditions, including metabolic acidosis, diabetes, sepsis, and high angiotensin II levels. Under these conditions, activation of muscle protein degradation requires endogenous glucocorticoids. As the mechanism(s) underlying this dependence on glucocorticoids have not been identified, we analyzed the effects of glucocorticoids on muscle wasting in a mouse model of acute diabetes. Adrenalectomized, acutely diabetic mice given a physiologic dose of glucocorticoids exhibited decreased IRS-1-associated PI3K activity in muscle and progressive muscle atrophy. These responses were related to increased association of PI3K with the glucocorticoid receptor (GR). In mice with muscle-specific GR deletion (referred to as MGRKO mice), acute diabetes minimally suppressed IRS-1-associated PI3K activity in muscle and did not cause muscle atrophy. However, when a physiologic dose of glucocorticoids was given to mice with muscle-specific IR deletion, muscle protein degradation was accelerated. Fluorescence resonance energy transfer and an in vitro competition assay revealed that activated GRs competed for PI3K, reducing its association with IRS-1. Reexpression of WT GRs or those with a mutation in the nuclear localization signal in the muscle of MGRKO mice indicated that competition for PI3K was a prominent mechanism underlying reduced IRS-1-associated PI3K activity. This nongenomic influence of the GR contributes to activation of muscle protein degradation. We therefore conclude that stimulation of muscle proteolysis requires 2 events, increased glucocorticoid levels and impaired insulin signaling.
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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.