ReviewFrontiers in immunology2019
Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macrophages Through Metabolic and Epigenetic Changes.
Review in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 85 citations in OpenAlex.
- Immunometabolism in Obesity-Associated Type 2 Diabetes: Molecular Mechanisms and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Trained immunity: New insights into pathogenesis and therapeutic targets in diabetes and diabetic complications.Genes & diseases · 2026Review
- IGF1-IGF1R signaling in tumor-associated macrophages regulates extracellular matrix organization in BRAF inhibitor-targeted melanoma.Molecular and cellular biochemistry · 2026Article
- Epigenetic and metabolic reprogramming of innate immune cells establishes immunological memory in the Schistosomiasis vector snail Biomphalaria glabrata.PLoS pathogens · 2026Article
- Interplay between obesity-associated insulin resistance and immune system through the lens of evolutionary medicine.Molecular metabolism · 2026Review
- Insulin potentiates lipopolysaccharide-induced IL-6 expression through epigenetic remodeling in adipocytes:Frontiers in immunology · 2026Article
- Diet supplementation with the macroalgaeFrontiers in nutrition · 2026Article
- Article
- Metaflammation's Role in Systemic Dysfunction in Obesity: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Modulation of Macrophage Polarization by Traditional Chinese Medicine in HFpEF: A Review of Mechanisms and Therapeutic Potentials.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The association between triglyceride-glucose index and related parameters and risk of tuberculosis infection in American adults under different glucose metabolic states: a cross-sectional study.BMC public health · 2025Article
- Recent Advances of Trained immunity in Macrophages.International journal of biological sciences · 2025Review
- Identification and Verification of a Prognostic Risk Signature in Oral Squamous Cell Carcinoma.Current topics in medicinal chemistry · 2025Article
- Therapeutic Insulin Analogue Concentrations at Infusion Sites Enhanced the Pro-Inflammatory Response and Apoptosis in an In Vitro Macrophage-Material Interaction Model.ACS pharmacology & translational science · 2024Article
- Diabetes and Osteoarthritis: Exploring the Interactions and Therapeutic Implications of Insulin, Metformin, and GLP-1-Based Interventions.Biomedicines · 2024Review
- Innate immune memory in cardiometabolic disease.Cardiovascular research · 2024Review
- Article
- Eating away cancer: the potential of diet and the microbiome for shaping immunotherapy outcome.Frontiers in immunology · 2024Review
- Immune-endocrine network in diabetes-tuberculosis nexus: does latent tuberculosis infection confer protection against meta-inflammation and insulin resistance?Frontiers in endocrinology · 2024Review
- In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4Vaccines · 2023Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptation of the innate immune system has been recently acknowledged, explaining sustained changes of innate immune responses. Such adaptation is termed trained immunity. Trained immunity is initiated by extracellular signals that trigger a cascade of events affecting cell metabolism and mediating chromatin changes on genes that control innate immune responses. Factors demonstrated to facilitate trained immunity are pathogenic signals (fungi, bacteria, viruses) as well non-pathogenic signals such as insulin, cytokines, adipokines or hormones. These signals initiate intracellular signaling cascades that include AKT kinases and mTOR as well as histone methylases and demethylases, resulting in metabolic changes and histone modifications. In the context of insulin resistance, AKT signaling is affected resulting in sustained activation of mTORC1 and enhanced glycolysis. In macrophages elevated glycolysis readily impacts responses to pathogens (bacteria, fungi) or danger signals (TLR-driven signals of tissue damage), partly explaining insulin resistance-related pathologies. Thus, macrophages lacking insulin signaling exhibit reduced responses to pathogens and altered metabolism, suggesting that insulin resistance is a state of trained immunity. Evidence from Insulin Receptor as well as IGF1Receptor deficient macrophages support the contribution of insulin signaling in macrophage responses. In addition, clinical evidence highlights altered macrophage responses to pathogens or metabolic products in patients with systemic insulin resistance, being in concert with cell culture and animal model studies. Herein, we review the current knowledge that supports the impact of insulin signaling and other insulin resistance related signals as modulators of trained immunity.
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