ArticleeLife2024
The genetic and dietary landscape of the muscle insulin signalling network.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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.
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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.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.The Journal of biological chemistry · 2026Review
- Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch-triggered calorie reduction.Science advances · 2026Article
- Sex-specific phosphoproteome responses to calorie restriction and insulin in skeletal muscle from older rats.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Genetic variance in the murine defensin locus modulates glucose homeostasis.The EMBO journal · 2025Article
- The insulin signalling network.Nature metabolism · 2025Review
- A biomimetic multimodal nanoplatform combining neutrophil-coated two-dimensional metalloporphyrinic framework nanosheet and exendin-4 to treat obesity-related osteoporosis.Materials today. Bio · 2025Article
- Skeletal muscle proteomics: considerations and opportunities.npj metabolic health and disease · 2025Review
- Serum Lipidome and Metabolome Alterations in Obese Patients Undergoing Targeted Diet and Exercise Interventions: A Marker of Thyroid Function Recovery?International journal of endocrinology · 2025Article
- Unlocking metabolic insights with mouse genetic diversity.The EMBO journal · 2024Article
- Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles.Communications biology · 2024Article
- Deletion of miPEP in adipocytes protects against obesity and insulin resistance by boosting muscle metabolism.Molecular metabolism · 2024Article
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Metabolic disease is caused by a combination of genetic and environmental factors, yet few studies have examined how these factors influence signal transduction, a key mediator of metabolism. Using mass spectrometry-based phosphoproteomics, we quantified 23,126 phosphosites in skeletal muscle of five genetically distinct mouse strains in two dietary environments, with and without acute in vivo insulin stimulation. Almost half of the insulin-regulated phosphoproteome was modified by genetic background on an ordinary diet, and high-fat high-sugar feeding affected insulin signalling in a strain-dependent manner. Our data revealed coregulated subnetworks within the insulin signalling pathway, expanding our understanding of the pathway's organisation. Furthermore, associating diverse signalling responses with insulin-stimulated glucose uptake uncovered regulators of muscle insulin responsiveness, including the regulatory phosphosite S469 on Pfkfb2, a key activator of glycolysis. Finally, we confirmed the role of glycolysis in modulating insulin action in insulin resistance. Our results underscore the significance of genetics in shaping global signalling responses and their adaptability to environmental changes, emphasising the utility of studying biological diversity with phosphoproteomics to discover key regulatory mechanisms of complex traits.
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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 Socratic graph.