ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2016
FOXO1 Mediates Vitamin D Deficiency-Induced Insulin Resistance in Skeletal Muscle.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 90 citations in OpenAlex.
- Cardiorenal Protective Effects of Finerenone in Patients with Type 2 Diabetes Mellitus.Archives of internal medicine research · 2026Article
- Vitamin D-Mediated Immunoregulation in Degenerative Diseases: Insights into Cardiovascular, Neurodegenerative and Musculoskeletal Disorders.Nutrients · 2026Review
- Association of vitamin D deficiency with insulin resistance among type 2 diabetes mellitus patients - A case-control study.Bioinformation · 2025Article
- Correlation analysis of thyroid function and vitamin D levels in patients with type 2 diabetes.Frontiers in endocrinology · 2025Article
- Exploring the Intersection of Diabetes and Musculoskeletal Health : Diabetes and Musculoskeletal Health.Galen medical journal · 2025Review
- Nutrition, Gut Microbiota, and Epigenetics in the Modulation of Immune Response and Metabolic Health.Cardiology and cardiovascular medicine · 2025Article
- Hepatocyte vitamin D receptor functions as a nutrient sensor that regulates energy storage and tissue growth in zebrafish.Cell reports · 2024Article
- Review
- High dose dietary vitamin D allocates surplus calories to muscle and growth instead of fat via modulation of myostatin and leptin signaling.Research square · 2024Article
- Etiology, Pathophysiology, and Treatment Strategies in the Prevention and Management of Metabolic Syndrome.Archives of internal medicine research · 2024Article
- Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes.Biomedicines · 2023Review
- The Role of Forkhead Box O in Pathogenesis and Therapy of Diabetes Mellitus.International journal of molecular sciences · 2022Review
- Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health.Biomedicines · 2022Review
- Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism.Nutrients · 2022Article
- Serum 25-hydroxy vitamin D and the risk of low muscle mass in young and middle-aged Korean adults.European journal of endocrinology · 2022Article
- Systemic ablation of vitamin D receptor leads to skeletal muscle glycogen storage disorder in mice.Journal of cachexia, sarcopenia and muscle · 2022Article
- VDR regulates simulated microgravity-induced atrophy in C2C12 myotubes.Scientific reports · 2022Article
- Mechanisms Linking Vitamin D Deficiency to Impaired Metabolism: An Overview.International journal of endocrinology · 2022Review
- Sirt1 Mediates Vitamin D Deficiency-Driven Gluconeogenesis in the Liver via mTorc2/Akt Signaling.Journal of diabetes research · 2022Article
- Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Prospective epidemiological studies have consistently shown a relationship between vitamin D deficiency, insulin resistance, and type 2 diabetes mellitus (DM2). This is supported by recent trials showing that vitamin D supplementation in prediabetic or insulin-resistant patients with inadequate vitamin D levels improves insulin sensitivity. However, the molecular mechanisms underlying vitamin D deficiency-induced insulin resistance and DM2 remain unknown. Skeletal muscle insulin resistance is a primary defect in the majority of patients with DM2. Although sustained activation of forkhead box O1 (FOXO1) in skeletal muscle causes insulin resistance, a relationship between vitamin D deficiency and FOXO1 activation in muscle is unknown. We generated skeletal muscle-specific vitamin D receptor (VDR)-null mice and discovered that these mice developed insulin resistance and glucose intolerance accompanied by increased expression and activity of FOXO1. We also found sustained FOXO1 activation in the skeletal muscle of global VDR-null mice. Treatment of C2C12 muscle cells with 1,25-dihydroxyvitamin D (VD3) reduced FOXO1 expression, nuclear translocation, and activity. The VD3-dependent suppression of FOXO1 activation disappeared by knockdown of VDR, indicating that it is VDR-dependent. Taken together, these results suggest that FOXO1 is a critical target mediating VDR-null signaling in skeletal muscle. The novel findings provide the conceptual support that persistent FOXO1 activation may be responsible for insulin resistance and impaired glucose metabolism in vitamin D signaling-deficient mice, as well as evidence for the utility of vitamin D supplementation for intervention in DM2.
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