ArticleDiabetologia2014
TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 128 citations in OpenAlex.
- Variants in transient receptor potential channels and toll-like receptors modify airway responses to allergen and air pollution: a randomized controlled response human exposure study.Respiratory research · 2023Trial
- Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic β-cell function in both African ancestry and European ancestry healthy humans.Metabolism: clinical and experimental · 2015Trial
- Toll-like receptor 2 modulates age-associated insulitis and fibrotic remodeling of Langerhans islets.Immunity & ageing : I & A · 2026Article
- Islet amyloid disrupts MHC class II antigen presentation and delays autoimmune diabetes in NOD mice.Diabetologia · 2026Article
- Mechanisms and Drug-Augmenting Strategies of Mesenchymal Stem Cells for Preserving β-Cell in Type 2 Diabetes.Drug design, development and therapy · 2026Review
- Role of Innate Immune Receptors in Cardiac Damage Linked to Metabolic Disorders.Handbook of experimental pharmacology · 2026Review
- The role of gut microbiome disruption in the development of metabolic dysfunction-associated kidney disease.Acta biochimica Polonica · 2026Review
- The role of pancreatic islet macrophages in type 2 diabetes mellitus: from underlying pathological mechanisms to therapeutic target discovery.Metabolism open · 2025Review
- Effect of lipotoxic hepatocyte-derived extracellular vesicles in pancreas inflammation: essential role of macrophage TLR4 in beta cell functionality.Diabetologia · 2025Article
- Immune cell-adipose tissue crosstalk in metabolic diseases with a focus on type 1 diabetes.Diabetologia · 2025Review
- Crumbling Pathogenesis and Biomarkers for Diabetic Peripheral Neuropathy.Biomedicines · 2025Review
- Treatment of T2DM-related inflammation and vascular injury by regulating cellular crosstalk in the islet microenvironment.Frontiers in endocrinology · 2025Review
- Asprosin: its function as a novel endocrine factor in metabolic-related diseases.Journal of endocrinological investigation · 2024Review
- STING signaling in islet macrophages impairs insulin secretion in obesity.Science China. Life sciences · 2024Article
- Phenotype similarities in automatically grouped T2D patients by variation-based clustering of IL-1β gene expression.EJIFCC · 2023Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Metformin, Empagliflozin, and Their Combination Modulate Ex-Vivo Macrophage Inflammatory Gene Expression.International journal of molecular sciences · 2023Article
- Islet amyloid polypeptide aggregation exerts cytotoxic and proinflammatory effects on the islet vasculature in mice.Diabetologia · 2022Article
- Islet Inflammation and β Cell Dysfunction in Type 2 Diabetes.Handbook of experimental pharmacology · 2022Review
- Chemical inducer of regucalcin attenuates lipopolysaccharide-induced inflammatory responses in pancreatic MIN6 β-cells and RAW264.7 macrophages.FEBS open bio · 2022Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
aims/hypothesisInflammation contributes to pancreatic beta cell dysfunction in type 2 diabetes. Toll-like receptor (TLR)-2 and -4 ligands are increased systemically in recently diagnosed type 2 diabetes patients, and TLR2- and TLR4-deficient mice are protected from the metabolic consequences of a high-fat diet. Here we investigated the role of macrophages in TLR2/6- and TLR4-mediated effects on islet inflammation and beta cell function.
methodsGenetic and pharmacological approaches were used to determine the effects of TLR2/6 and TLR4 ligands on mouse islets, human islets and purified rat beta cells. Islet macrophages were depleted and sorted by flow cytometry and the effects of TLR2/6- and TLR4-activated bone-marrow-derived macrophages (BMDMs) on beta cell function were assessed.
resultsMacrophages contributed to TLR2/6- and TLR4-induced islet Il1a/IL1A and Il1b/IL1B mRNA expression in mouse and human islets and IL-1β secretion from human islets. TLR2/6 and TLR4 ligands also reduced insulin gene expression; however, this occurred in a non-beta cell autonomous manner. TLR2/6- and TLR4-activated BMDMs reduced beta cell insulin secretion partly via reducing Ins1, Ins2, and Pdx1 mRNA expression. Antagonism of the IL-1 receptor and neutralisation of IL-6 completely reversed the effects of activated macrophages on beta cell gene expression. CONCLUSIONS/
interpretationWe conclude that islet macrophages are major contributors to islet IL-1β secretion in response to TLR2/6 and TLR4 ligands. BMDMs stimulated with TLR2/6 and TLR4 ligands reduce insulin secretion from pancreatic beta cells, partly via IL-1β- and IL-6-mediated decreased insulin gene 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.