ArticleFrontiers in physiology2021
Transcriptomic Regulation of Muscle Mitochondria and Calcium Signaling by Insulin/IGF-1 Receptors Depends on FoxO Transcription Factors.
Article in Frontiers in physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- Plant‑derived natural products alleviate dexamethasone‑induced skeletal muscle atrophy by modulating FoxO (Review).International journal of molecular medicine · 2026Review
- Brain senescence drives sarcopenia-like transcriptomic remodeling in skeletal muscle.GeroScience · 2026Article
- Loss of FoxO in skeletal muscle leads to disrupted muscle metabolism and exacerbates starvation-induced hepatic steatosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- IGF1R deficiency mitigates acute lung injury by promoting anti-inflammatory transcriptional profiles.Respiratory research · 2025Article
- Temporal phosphoproteomics reveals circuitry of phased propagation in insulin signaling.Nature communications · 2025Article
- Skeletal Muscle mRNA Splicing Variants Association With Four Different Fitness and Energetic Measures in the GESTALT Study.Journal of cachexia, sarcopenia and muscle · 2025Article
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- Contrasting consequences of podocyte insulin-like growth factor 1 receptor inhibition.iScience · 2024Article
- Dexamethasone-induced muscle atrophy and bone loss in six genetically diverse collaborative cross founder strains demonstrates phenotypic variability by Rg3 treatment.Journal of ginseng research · 2024Article
- Normobaric hypoxia shows enhanced FOXO1 signaling in obese mouse gastrocnemius muscle linked to metabolism and muscle structure and neuromuscular innervation.Pflugers Archiv : European journal of physiology · 2023Article
- Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge.International journal of molecular sciences · 2023Review
- Loss of FoxOs in muscle increases strength and mitochondrial function during aging.Journal of cachexia, sarcopenia and muscle · 2023Article
- An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats.Frontiers in endocrinology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
Insulin and IGF-1, acting through the insulin receptor (IR) and IGF-1 receptor (IGF1R), maintain muscle mass and mitochondrial function, at least part of which occurs via their action to regulate gene expression. Here, we show that while muscle-specific deletion of IR or IGF1R individually results in only modest changes in the muscle transcriptome, combined deletion of IR/IGF1R (MIGIRKO) altered > 3000 genes, including genes involved in mitochondrial dysfunction, fibrosis, cardiac hypertrophy, and pathways related to estrogen receptor, protein kinase A (PKA), and calcium signaling. Functionally, this was associated with decreased mitochondrial respiration and increased ROS production in MIGIRKO muscle. To determine the role of FoxOs in these changes, we performed RNA-Seq on mice with muscle-specific deletion of FoxO1/3/4 (M-FoxO TKO) or combined deletion of IR, IGF1R, and FoxO1/3/4 in a muscle quintuple knockout (M-QKO). This revealed that among IR/IGF1R regulated genes, >97% were FoxO-dependent, and their expression was normalized in M-FoxO TKO and M-QKO muscle. FoxO-dependent genes were related to oxidative phosphorylation, inflammatory signaling, and TCA cycle. Metabolomic analysis showed accumulation of TCA cycle metabolites in MIGIRKO, which was reversed in M-QKO muscle. Likewise, calcium signaling genes involved in PKA signaling and sarcoplasmic reticulum calcium homeostasis were markedly altered in MIGIRKO muscle but normalized in M-QKO. Thus, combined loss of insulin and IGF-1 action in muscle transcriptionally alters mitochondrial function and multiple regulatory and signaling pathways, and these changes are mediated by FoxO transcription factors.
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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.