ArticleDiabetes2011
Cannabinoids inhibit insulin receptor signaling in pancreatic β-cells.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 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
- Acute metabolic effects of cannabinoid receptor modulators during sequential hyperglycemic, euglycemic-hyperinsulinemic clamps in healthy individuals.American journal of physiology. Endocrinology and metabolism · 2026Trial
- The endocannabinoid signaling system in acute and chronic pancreatitis.Frontiers in physiology · 2026Review
- Pharmaceutical targeting of the cannabinoid type 1 receptor impacts the crosstalk between immune cells and islets to reduce insulitis in humans.Diabetologia · 2024Article
- Effects of prenatal THC vapor exposure on body weight, glucose metabolism, and feeding behaviors in chow and high-fat diet fed rats.International journal of obesity (2005) · 2024Article
- Cannabinoids Block Fat-induced Incretin Release via CBGastro hep advances · 2024Article
- Article
- Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity.Biomedicines · 2023Review
- Review
- Role of the Endocannabinoid System in Metabolic Control Processes and in the Pathogenesis of Metabolic Syndrome: An Update.Biomedicines · 2023Review
- The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease.International journal of molecular sciences · 2022Review
- Nampt activator P7C3 ameliorates diabetes and improves skeletal muscle function modulating cell metabolism and lipid mediators.Journal of cachexia, sarcopenia and muscle · 2022Article
- The Peripheral Cannabinoid Receptor Type 1 (CBMolecules (Basel, Switzerland) · 2021Review
- The Impact of Early Life Exposure to Cannabis: The Role of the Endocannabinoid System.International journal of molecular sciences · 2021Review
- Review
- Direct Stimulatory Effects of the CBCells · 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
- Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveOptimal glucose homeostasis requires exquisitely precise adaptation of the number of insulin-secreting β-cells in the islets of Langerhans. Insulin itself positively regulates β-cell proliferation in an autocrine manner through the insulin receptor (IR) signaling pathway. It is now coming to light that cannabinoid 1 receptor (CB1R) agonism/antagonism influences insulin action in insulin-sensitive tissues. However, the cells on which the CB1Rs are expressed and their function in islets have not been firmly established. We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate β-cell proliferation and if they influence insulin action. RESEARCH DESIGN AND
methodsWe measured EC production in isolated human and mouse islets and β-cell line in response to glucose and KCl. We evaluated human and mouse islets, several β-cell lines, and CB1R-null (CB1R(-/-)) mice for the presence of a fully functioning EC system. We investigated if ECs influence β-cell physiology through regulating insulin action and demonstrated the therapeutic potential of manipulation of the EC system in diabetic (db/db) mice.
resultsECs are generated within β-cells, which also express CB1Rs that are fully functioning when activated by ligands. Genetic and pharmacologic blockade of CB1R results in enhanced IR signaling through the insulin receptor substrate 2-AKT pathway in β-cells and leads to increased β-cell proliferation and mass. CB1R antagonism in db/db mice results in reduced blood glucose and increased β-cell proliferation and mass, coupled with enhanced IR signaling in β-cells. Furthermore, CB1R activation impedes insulin-stimulated IR autophosphorylation on β-cells in a Gα(i)-dependent manner.
conclusionsThese findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of β-cell proliferation and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and proliferation in diabetes.
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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.