ArticleNature medicine2013
Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
232 citing papers in PubMed, 1 synthesis or guideline pooled it, 403 citations in OpenAlex.
- Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.International journal of molecular sciences · 2020Pooled it
- The effects of acute alcohol administration on circulating endocannabinoid levels in humans.Addiction biology · 2022Trial
- Targeting Cannabinoid 1 Receptor in Macrophages Alleviates Psoriatic Skin Inflammation Through the AUF1-NLRP3 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial cannabinoid CB1 receptor deficiency reduces shear stress-induced arterial inflammation and lipid uptake.Nature communications · 2026Article
- Review
- The role of immunoproteasome in diabetes and diabetes-related complications.Genes & diseases · 2026Review
- Microbiota-Gut-Brain Axis Disruption, Neuroinflammation, and Potential Antioxidant-Based Treatments in Metabolic Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Current Landscape of the Interrelationship Between Periodontitis, Type 2 Diabetes Mellitus, and COVID-19.International journal of molecular sciences · 2025Review
- Review
- Inhibitory effects of the flavonoids extracted from Pollen Typhae on palmitic acid-induced NLRP3 inflammasome activation in macrophages involving AMPK-mediated lipid metabolism.BMC complementary medicine and therapies · 2025Article
- Targeting cannabinoid receptor 1 for antagonism in pro-fibrotic alveolar macrophages mitigates pulmonary fibrosis.JCI insight · 2025Article
- Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.Cannabis and cannabinoid research · 2025Article
- Interactions between islet-resident macrophages and β cells in diabetes.Frontiers in immunology · 2025Review
- Interplay Between Insulin Resistance and Immune Dysregulation in Type 2 Diabetes Mellitus: Implications for Therapeutic Interventions.ImmunoTargets and therapy · 2025Review
- Review
- Relationship between periodontitis, type 2 diabetes mellitus and COVID-19 disease: a narrative review.Frontiers in cellular and infection microbiology · 2025Review
- Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner.Cardiovascular research · 2024Article
- The effect and mechanism of freeze-dried powder ofHeliyon · 2024Article
- Pharmaceutical targeting of the cannabinoid type 1 receptor impacts the crosstalk between immune cells and islets to reduce insulitis in humans.Diabetologia · 2024Article
- Bibliometric study of sepsis-associated liver injury from 2000 to 2023.World journal of gastroenterology · 2024Article
172 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Type 2 diabetes mellitus (T2DM) progresses from compensated insulin resistance to beta cell failure resulting in uncompensated hyperglycemia, a process replicated in the Zucker diabetic fatty (ZDF) rat. The Nlrp3 inflammasome has been implicated in obesity-induced insulin resistance and beta cell failure. Endocannabinoids contribute to insulin resistance through activation of peripheral CB1 receptors (CB₁Rs) and also promote beta cell failure. Here we show that beta cell failure in adult ZDF rats is not associated with CB₁R signaling in beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages. These effects are replicated in vitro by incubating wild-type human or rodent macrophages, but not macrophages from CB₁R-deficient (Cnr1(-/-)) or Nlrp3(-/-) mice, with the endocannabinoid anandamide. Peripheral CB₁R blockade, in vivo depletion of macrophages or macrophage-specific knockdown of CB₁R reverses or prevents these changes and restores normoglycemia and glucose-induced insulin secretion. These findings implicate endocannabinoids and inflammasome activation in beta cell failure and identify macrophage-expressed CB₁R as a therapeutic target in T2DM.
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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.