ArticleJCI insight2021
Adipocyte P2Y14 receptors play a key role in regulating whole-body glucose and lipid homeostasis.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Purinergic signaling in osteoarthritis: Mechanistic insights into pathogenesis and therapeutic targeting.Genes & diseases · 2026Review
- Adipocyte-specific NR5A2 deficiency ameliorates diet-induced metabolic syndrome by suppressing adipose tissue inflammation.Scientific reports · 2026Article
- UDP-glucose and MRS2905 agonist-bound states of the purinergic P2YCommunications biology · 2025Article
- Saliva as a potential and non-invasive approach to identify upregulated genes associated with comorbidities of T1DM: a brief report.European journal of medical research · 2025Article
- P2YACS pharmacology & translational science · 2025Article
- Structural insights into ligand recognition and activation of human purinergic receptor P2Y14.Cell discovery · 2025Article
- UDP-glucose regulates dendritic cell mitochondrial respiration via a nitric oxide-dependent mechanism.Journal of leukocyte biology · 2025Article
- E. B. Hershberg Award: Taming Inflammation by Tuning Purinergic Signaling.Accounts of chemical research · 2025Article
- Chimeras Derived from a P2YACS pharmacology & translational science · 2024Article
- P2Y13 receptor deficiency favors adipose tissue lipolysis and worsens insulin resistance and fatty liver disease.JCI insight · 2024Article
- Alicyclic Ring Size Variation of 4-Phenyl-2-naphthoic Acid Derivatives as P2YJournal of medicinal chemistry · 2023Article
- Article
- Purinergic receptor: a crucial regulator of adipose tissue functions.Purinergic signalling · 2023Review
- Knockout of Purinergic P2YInternational journal of molecular sciences · 2023Article
- Adipocyte purinergic receptors activated by uracil nucleotides as obesity and type 2 diabetes targets.Current opinion in pharmacology · 2022Review
- Bridged Piperidine Analogues of a High Affinity Naphthalene-Based P2YJournal of medicinal chemistry · 2022Article
- Adenosine ABiochemical pharmacology · 2021Article
- Purinergic Signaling in Liver Pathophysiology.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Obesity is the major driver of the worldwide epidemic in type 2 diabetes (T2D). In the obese state, chronically elevated plasma free fatty acid levels contribute to peripheral insulin resistance, which can ultimately lead to the development of T2D. For this reason, drugs that are able to regulate lipolytic processes in adipocytes are predicted to have considerable therapeutic potential. Gi-coupled P2Y14 receptor (P2Y14R; endogenous agonist, UDP-glucose) is abundantly expressed in both mouse and human adipocytes. Because activated Gi-type G proteins exert an antilipolytic effect, we explored the potential physiological relevance of adipocyte P2Y14Rs in regulating lipid and glucose homeostasis. Metabolic studies indicate that the lack of adipocyte P2Y14R enhanced lipolysis only in the fasting state, decreased body weight, and improved glucose tolerance and insulin sensitivity. Mechanistic studies suggested that adipocyte P2Y14R inhibits lipolysis by reducing lipolytic enzyme activity, including ATGL and HSL. In agreement with these findings, agonist treatment of control mice with a P2Y14R agonist decreased lipolysis, an effect that was sensitive to inhibition by a P2Y14R antagonist. In conclusion, we demonstrate that adipose P2Y14Rs were critical regulators of whole-body glucose and lipid homeostasis, suggesting that P2Y14R antagonists might be beneficial for the therapy of obesity and T2D.
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Registered trials
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