ArticleScience signaling2012
Cannabinoids induce pancreatic β-cell death by directly inhibiting insulin receptor activation.
Article in Science signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Cannabinoid-Related Acute Pancreatitis: An Update from International Literature and Individual Case Safety Reports.Drug safety · 2022Pooled it
- The Impact of Major and Minor Phytocannabinoids on the Maintenance and Function of INS-1 β-Cells Under High-Glucose and High-Lipid Conditions.Molecules (Basel, Switzerland) · 2025Article
- Interplay Between Insulin Resistance and Immune Dysregulation in Type 2 Diabetes Mellitus: Implications for Therapeutic Interventions.ImmunoTargets and therapy · 2025Review
- Developmental programming: Testosterone excess masculinizes female pancreatic transcriptome and function in sheep.Molecular and cellular endocrinology · 2024Article
- Gestational exposure to cannabidiol leads to glucose intolerance in 3-month-old male offspring.The Journal of endocrinology · 2024Article
- Cannabinoids Block Fat-induced Incretin Release via CBGastro hep advances · 2024Article
- Article
- Concerns Related to the Consequences of Pediatric Cannabis Use: A 360-Degree View.Children (Basel, Switzerland) · 2023Review
- Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity.Biomedicines · 2023Review
- Metabolic Messengers: endocannabinoids.Nature metabolism · 2022Review
- Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study.The Journal of clinical endocrinology and metabolism · 2022Article
- The Peripheral Cannabinoid Receptor Type 1 (CBMolecules (Basel, Switzerland) · 2021Review
- CB1 Cannabinoid Receptor Signaling and Biased Signaling.Molecules (Basel, Switzerland) · 2021Review
- Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes.Cell reports · 2021Article
- Role of the Endocannabinoid System in the Adipose Tissue with Focus on Energy Metabolism.Cells · 2021Review
- Endocannabinoids Produced by White Adipose Tissue Modulate Lipolysis in Lean but Not in Obese Rodent and Human.Frontiers in endocrinology · 2021Article
- Chronic marijuana usage by human pancreas donors is associated with impaired islet function.PloS one · 2021Article
- An Autonomous Cannabinoid System in Islets of Langerhans.Frontiers in endocrinology · 2021Review
- The cannabinoid ligands SR141716A and AM251 enhance human and mouse islet function via GPR55-independent signalling.Cellular and molecular life sciences : CMLS · 2020Article
- The effects of recreational cannabis use on glycemic outcomes and self-management behaviours in people with type 1 and type 2 diabetes: a rapid review.Systematic reviews · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Cannabinoid 1 (CB1) receptors have been previously detected in pancreatic β cells, where they attenuate insulin action. We now report that CB1 receptors form a heteromeric complex with insulin receptors and the heterotrimeric guanosine triphosphate-binding protein α subunit Gα(i). Gα(i) inhibited the kinase activity of the insulin receptor in β cells by directly binding to the activation loop in the tyrosine kinase domain of the receptor. Consequently, phosphorylation of proapoptotic protein Bad was reduced and its apoptotic activity was stimulated, leading to β-cell death. Pharmacological blockade or genetic deficiency of CB1 receptors enhanced insulin receptor signaling after injury, leading to reduced blood glucose concentrations and activation of Bad, which increased β-cell survival. These findings provide direct evidence of physical and functional interactions between CB1 and insulin receptors and suggest a mechanism whereby peripherally acting CB1 receptor antagonists improve insulin action in insulin-sensitive tissues independent of the other metabolic effects of CB1 receptors.
Indexed as
Identifiers
What OpenQuestion holds
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.