ArticleDiabetologia2016
Metabolic effects of orally administered small-molecule agonists of GPR55 and GPR119 in multiple low-dose streptozotocin-induced diabetic and incretin-receptor-knockout mice.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Acute Effects of Cannabinoid Combination Therapies in a Western Diet-Induced Murine Model of Metabolic Liver Disease.International journal of molecular sciences · 2026Article
- Fatty Acid-Sensing G Protein-Coupled Receptors in Skeletal Metabolism.Journal of bone metabolism · 2026Article
- Anti-inflammatory effects of cannabidiol in the treatment of type 1 diabetes: A mini review.World journal of diabetes · 2025Review
- A Phase I Randomized, Double-blind, Placebo-controlled Study on Efficacy and Safety Profile of a Sublingually Administered Cannabidiol /Delta 9-tetrahydrocannabidiol (10: 1) Regimen in Diabetes Type 2 Patients.Iranian journal of pharmaceutical research : IJPR · 2022Article
- Novel Noninvasive Approaches to the Treatment of Obesity: From Pharmacotherapy to Gene Therapy.Endocrine reviews · 2022Review
- GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Targeting lipid GPCRs to treat type 2 diabetes mellitus - progress and challenges.Nature reviews. Endocrinology · 2021Review
- The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease.International journal of molecular sciences · 2020Review
- Article
- Oleoylethanolamide Exhibits GPR119-Dependent Inhibition of Osteoclast Function and GPR119-Independent Promotion of Osteoclast Apoptosis.Molecules and cells · 2020Article
- The Atypical Cannabinoid Abn-CBD Reduces Inflammation and Protects Liver, Pancreas, and Adipose Tissue in a Mouse Model of Prediabetes and Non-alcoholic Fatty Liver Disease.Frontiers in endocrinology · 2020Article
- Rapid and Concomitant Gut Microbiota and Endocannabinoidome Response to Diet-Induced Obesity in Mice.mSystems · 2019Article
- The Expanded Endocannabinoid System/Endocannabinoidome as a Potential Target for Treating Diabetes Mellitus.Current diabetes reports · 2019Review
- Atypical cannabinoid ligands O-1602 and O-1918 administered chronically in diet-induced obesity.Endocrine connections · 2019Article
- Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats.Neurotoxicity research · 2019Article
- Role of Hippocampal Lipocalin-2 in Experimental Diabetic Encephalopathy.Frontiers in endocrinology · 2019Article
- Potential metabolic and behavioural roles of the putative endocannabinoid receptors GPR18, GPR55 and GPR119 in feeding.Current neuropharmacology · 2019Review
- The Bile Acid TUDCA Improves Beta-Cell Mass and Reduces Insulin Degradation in Mice With Early-Stage of Type-1 Diabetes.Frontiers in physiology · 2019Article
- Endocannabinoids in the Islets of Langerhans: the ugly, the bad, and the good facts.American journal of physiology. Endocrinology and metabolism · 2018Review
- An Overview on Medicinal Chemistry of Synthetic and Natural Derivatives of Cannabidiol.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisAbnormal cannabidiol (Abn-CBD) and AS-1269574 are potent selective agonists for GPR55 and GPR119, respectively. The present study evaluated the actions and ability of these small-molecule agonists to counteract experimental diabetes in mice.
methodsDiabetes was induced in NIH Swiss mice by five consecutive daily intraperitoneal injections of 40 mg/(kg body weight) streptozotocin. Diabetic mice received daily oral administration of Abn-CBD or AS-1269574 (0.1 μmol/kg) or saline vehicle (0.9% wt/vol. NaCl) over 28 days. Body weight, food intake, fluid intake, plasma glucose, insulin, glucose tolerance, insulin release, lipid profile and pancreatic morphology were examined. Mechanism of action of agonists was assessed in acute studies using incretin-receptor-knockout mice.
resultsAbn-CBD and AS-1269574 decreased plasma glucose (20-26%, p < 0.05) and increased circulating insulin (47-48%, p < 0.05) by 10-28 days, compared with saline-treated diabetic controls. Food intake and polydipsia were reduced by both agonists (21-23%, p < 0.05 and 33-35%, p < 0.01, respectively). After 28 days of treatment, plasma glucagon concentrations were reduced (p < 0.01) and glucose tolerance was enhanced by 19-44% by Abn-CBD (p < 0.05 or p < 0.001) and AS-1269574 (p < 0.05 to p < 0.001). Plasma insulin responses were improved (p < 0.01) and insulin resistance was decreased (p < 0.05 or p < 0.01) in both Abn-CBD- and AS-1269574-treated groups. Triacylglycerols were decreased by 19% with Abn-CBD (p < 0.05) and 32% with AS-1269574 (p < 0.01) while total cholesterol was reduced by 17% (p < 0.01) and 15% (p < 0.05), respectively. Both agonists enhanced beta cell proliferation (p < 0.001) although islet area was unchanged. Acute studies in Gipr- and Glp1r-knockout mice revealed an important role for the glucagon-like peptide 1 (GLP-1) receptor in the actions of both agonists, with the glucose-lowering effects of Abn-CBD also partly mediated through the glucose-dependent insulinotropic peptide (GIP) receptor. CONCLUSIONS/
interpretationThese data highlight the potential for fatty acid G-protein-coupled receptor-based therapies as novel insulinotropic and glucose-lowering agents acting partly through the activation of incretin receptors.
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