ArticleThe Journal of clinical endocrinology and metabolism2015
Variation in glucose homeostasis traits associated with P2RX7 polymorphisms in mice and humans.
Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Association of P2X7 polymorphisms on Type 2 diabetes mellitus susceptibility and diabetic complications.PloS one · 2025Article
- P2X7 Variants in Pathophysiology.International journal of molecular sciences · 2024Review
- Human P2X7 receptor variants Gly150Arg and Arg276His polymorphisms have differential effects on risk association and cellular functions in pancreatic cancer.Cancer cell international · 2024Article
- Comorbidity Genes of Alzheimer's Disease and Type 2 Diabetes Associated with Memory and Cognitive Function.International journal of molecular sciences · 2024Review
- Animal Models for the Investigation of P2X7 Receptors.International journal of molecular sciences · 2023Review
- The Purinergic Landscape of Type 2 Diabetes Mellitus.Molecules (Basel, Switzerland) · 2022Review
- To inhibit or to boost the ATP/P2RX7 pathway to fight cancer-that is the question.Purinergic signalling · 2021Review
- Relationship betweenIranian journal of public health · 2021Article
- P2X7 Receptor Activity Limits Accumulation of T Cells within Tumors.Cancer research · 2020Article
- Update of P2Y receptor pharmacology: IUPHAR Review 27.British journal of pharmacology · 2020Review
- Ion Channels of the Islets in Type 2 Diabetes.Journal of molecular biology · 2020Review
- P2X7 Receptor in the Management of Energy Homeostasis: Implications for Obesity, Dyslipidemia, and Insulin Resistance.Frontiers in endocrinology · 2020Review
- Enrichment of intestinal Lactobacillus by enhanced secretory IgA coating alters glucose homeostasis in P2rx7Scientific reports · 2019Article
- Islet-Derived eATP Fuels Autoreactive CD8Diabetes · 2018Article
- The P2X7 receptor and pannexin-1 are involved in glucose-induced autocrine regulation in β-cells.Scientific reports · 2018Article
- Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes.Nature communications · 2018Article
- The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?Frontiers in pharmacology · 2018Review
- Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation.Frontiers in pharmacology · 2018Review
- T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP.Cell reports · 2017Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
Abstract
contextExtracellular nucleotide receptors are expressed in pancreatic B-cells. Purinergic signaling via these receptors may regulate pancreatic B-cell function.
objectiveWe hypothesized that purinergic signaling might influence glucose regulation and sought evidence in human studies of glycemic variation and a mouse model of purinergic signaling dysfunction.
designIn humans, we mined genome-wide meta-analysis data sets to examine purinergic signaling genes for association with glycemic traits and type 2 diabetes. We performed additional testing in two genomic regions (P2RX4/P2RX7 and P2RY1) in a cohort from the Prevalence, Prediction, and Prevention of Diabetes in Botnia (n = 3504), which includes more refined measures of glucose homeostasis. In mice, we generated a congenic model of purinergic signaling dysfunction by crossing the naturally hypomorphic C57BL6 P2rx7 allele onto the 129SvJ background.
resultsVariants in five genes were associated with glycemic traits and in three genes with diabetes risk. In the Prevalence, Prediction, and Prevention of Diabetes in Botnia study, the minor allele in the missense functional variant rs1718119 (A348T) in P2RX7 was associated with increased insulin sensitivity and secretion, consistent with its known effect on increased pore function. Both male and female P2x7-C57 mice demonstrated impaired glucose tolerance compared with matched P2x7-129 mice. Insulin tolerance testing showed that P2x7-C57 mice were also less responsive to insulin than P2x7-129 mice.
conclusionsWe show association of the purinergic signaling pathway in general and hypofunctioning P2X7 variants in particular with impaired glucose homeostasis in both mice and humans.
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