ArticleThe Journal of clinical investigation2021
Insulin and IGF-1 receptors regulate complex I-dependent mitochondrial bioenergetics and supercomplexes via FoxOs in muscle.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Efficacy ofNutrients · 2024Trial
- Article
- Plant‑derived natural products alleviate dexamethasone‑induced skeletal muscle atrophy by modulating FoxO (Review).International journal of molecular medicine · 2026Review
- Brown fat-specific RNA labelling reveals a network of inter-organ communication by secreted microRNAs.Nature metabolism · 2026Article
- Brain senescence drives sarcopenia-like transcriptomic remodeling in skeletal muscle.GeroScience · 2026Article
- Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?The Journal of biological chemistry · 2026Review
- The allostatic triage model of psychopathology (ATP Model): How reallocation of brain energetic resources under stress elicits psychiatric symptoms.Neuroscience and biobehavioral reviews · 2025Review
- Machine learning-based stratification of prediabetes and type 2 diabetes progression.Diabetology & metabolic syndrome · 2025Article
- Exploring the Intersection of Diabetes and Musculoskeletal Health : Diabetes and Musculoskeletal Health.Galen medical journal · 2025Review
- The Roles of Forkhead Box O3a (FOXO3a) in Bone and Cartilage Diseases - A Narrative Review.Drug design, development and therapy · 2025Review
- Adipose-derived exosomes ameliorate skeletal muscle atrophy via miR-146a-5p/IGF-1R signaling.Journal of nanobiotechnology · 2024Article
- Podocyte senescence: from molecular mechanisms to therapeutics.Renal failure · 2024Review
- Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease.Nature communications · 2024Article
- Ovarian aging: energy metabolism of oocytes.Journal of ovarian research · 2024Review
- Contrasting consequences of podocyte insulin-like growth factor 1 receptor inhibition.iScience · 2024Article
- Skeletal muscle myosin heavy chain expression and 3D capillary network changes in streptozotocin-induced diabetic female mice.Biomolecules & biomedicine · 2024Article
- Placenta-derived exosomal miR-135a-5p promotes gestational diabetes mellitus pathogenesis by activating PI3K/AKT signalling pathway via SIRT1.Journal of cellular and molecular medicine · 2023Article
- Mitochondrial dysfunction: roles in skeletal muscle atrophy.Journal of translational medicine · 2023Review
- Gene Therapy Strategies Targeting Aging-Related Diseases.Aging and disease · 2023Review
- Chronic Kidney Disease is Associated With Attenuated Plasma Metabolome Response to Oral Glucose Tolerance Testing.Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation · 2023Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Decreased skeletal muscle strength and mitochondrial dysfunction are characteristic of diabetes. The actions of insulin and IGF-1 through the insulin receptor (IR) and IGF-1 receptor (IGF1R) maintain muscle mass via suppression of forkhead box O (FoxO) transcription factors, but whether FoxO activation coordinates atrophy in concert with mitochondrial dysfunction is unknown. We show that mitochondrial respiration and complex I activity were decreased in streptozotocin (STZ) diabetic muscle, but these defects were reversed in muscle-specific FoxO1, -3, and -4 triple-KO (M-FoxO TKO) mice rendered diabetic with STZ. In the absence of systemic glucose or lipid abnormalities, muscle-specific IR KO (M-IR-/-) or combined IR/IGF1R KO (MIGIRKO) impaired mitochondrial respiration, decreased ATP production, and increased ROS. These mitochondrial abnormalities were not present in muscle-specific IR, IGF1R, and FoxO1, -3, and -4 quintuple-KO mice (M-QKO). Acute tamoxifen-inducible deletion of IR and IGF1R also decreased muscle pyruvate respiration, complex I activity, and supercomplex assembly. Although autophagy was increased when IR and IGF1R were deleted in muscle, mitophagy was not increased. Mechanistically, RNA-Seq revealed that complex I core subunits were decreased in STZ-diabetic and MIGIRKO muscle, and these changes were not present with FoxO KO in STZ-FoxO TKO and M-QKO mice. Thus, insulin-deficient diabetes or loss of insulin/IGF-1 action in muscle decreases complex I-driven mitochondrial respiration and supercomplex assembly in part by FoxO-mediated repression of complex I subunit expression.
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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.