ArticlePloS one2012
The A2b adenosine receptor modulates glucose homeostasis and obesity.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 111 citations in OpenAlex.
- An adenosine receptor-Krüppel-like factor 4 protein axis inhibits adipogenesis.The Journal of biological chemistry · 2014Trial
- Effect of Adenosine on the Morphological and Functional Integrity of Isolated Human Islets Exposed to Normoxic and Hypoxic Conditions.Bioengineering (Basel, Switzerland) · 2026Article
- Recent advances in methotrexate pharmacology and potential therapeutic uses in age-related cardiometabolic and neurodegenerative diseases.Pharmacological reviews · 2026Review
- Special Issue "Molecular Research on Adenosine Receptors: From Cell Biology to Human Diseases".International journal of molecular sciences · 2025Article
- Non-Canonical Functions of Adenosine Receptors: Emerging Roles in Metabolism, Immunometabolism, and Epigenetic Regulation.International journal of molecular sciences · 2025Review
- APurinergic signalling · 2025Review
- Effects of Pulsed Electromagnetic Field Treatment on Skeletal Muscle Tissue Recovery in a Rat Model of Collagenase-Induced Tendinopathy: Results from a Proteome Analysis.International journal of molecular sciences · 2024Article
- Adenosine and adenosine receptors in metabolic imbalance-related neurological issues.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- A crucial role of adenosine deaminase in regulating gluconeogenesis in mice.The Journal of biological chemistry · 2024Article
- Depletion of hepatic glutathione and adenosine by glucocorticoid exposure in Wistar rats is pregnancy-independent.Toxicology reports · 2024Article
- Purinergic Signaling and its Role in the Stem Cell Differentiation.Mini reviews in medicinal chemistry · 2024Review
- Dual ABMC endocrine disorders · 2023Article
- Purinergic receptor: a crucial regulator of adipose tissue functions.Purinergic signalling · 2023Review
- Molecular Changes in Cells of Patients with Type 2 Diabetes Mellitus Depending on Changes in Glycemia Level in the Context of Lifestyle-An Overview of the Latest Scientific Discoveries.Current issues in molecular biology · 2023Review
- Knockout of Purinergic P2YInternational journal of molecular sciences · 2023Article
- Role of purinergic signalling in obesity-associated end-organ damage: focus on the effects of natural plant extracts.Frontiers in endocrinology · 2023Review
- Preliminary Evidence of the Potent and Selective Adenosine A2B Receptor Antagonist PSB-603 in Reducing Obesity and Some of Its Associated Metabolic Disorders in Mice.International journal of molecular sciences · 2022Article
- The purinergic signalling and inflammation in the pathogenesis and progression of diabetes: key factors and therapeutic targets.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Metabolomics Provides Insights into Renoprotective Effects of Semaglutide in Obese Mice.Drug design, development and therapy · 2022Article
- Alternative adenosine Receptor activation: The netrin-Adora2b link.Frontiers in pharmacology · 2022Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHigh fat diet and its induced changes in glucose homeostasis, inflammation and obesity continue to be an epidemic in developed countries. The A2b adenosine receptor (A2bAR) is known to regulate inflammation. We used a diet-induced obesity murine knockout model to investigate the role of this receptor in mediating metabolic homeostasis, and correlated our findings in obese patient samples. METHODOLOGY/PRINCIPAL
findingsAdministration of high fat, high cholesterol diet (HFD) for sixteen weeks vastly upregulated the expression of the A2bAR in control mice, while A2bAR knockout (KO) mice under this diet developed greater obesity and hallmarks of type 2 diabetes (T2D), assessed by delayed glucose clearance and augmented insulin levels compared to matching control mice. We identified a novel link between the expression of A2bAR, insulin receptor substrate 2 (IRS-2), and insulin signaling, determined by Western blotting for IRS-2 and tissue Akt phosphorylation. The latter is impaired in tissues of A2bAR KO mice, along with a greater inflammatory state. Additional mechanisms involved include A2bAR regulation of SREBP-1 expression, a repressor of IRS-2. Importantly, pharmacological activation of the A2bAR by injection of the A2bAR ligand BAY 60-6583 for four weeks post HFD restores IRS-2 levels, and ameliorates T2D. Finally, in obese human subjects A2bAR expression correlates strongly with IRS-2 expression. CONCLUSIONS/SIGNIFICANCE: Our study identified the A2bAR as a significant regulator of HFD-induced hallmarks of T2D, thereby pointing to its therapeutic potential.
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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.