ArticlePurinergic signalling2013
High glucose and free fatty acids induce beta cell apoptosis via autocrine effects of ADP acting on the P2Y(13) receptor.
Article in Purinergic signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 32 citations in OpenAlex.
- Predictive Value of Incorporating Principal Diagnosis into CGA for Short-Term Functional Recovery in an ACE Unit: A Retrospective Study.Clinical interventions in aging · 2026Article
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- Diabetes and hypertension: Pivotal involvement of purinergic signaling.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2021Review
- Telmisartan Potentiates Insulin Secretion via Ion Channels, Independent of the AT1 Receptor and PPARγ.Frontiers in pharmacology · 2021Article
- Pannexin 1 inhibition delays maturation and improves development of Bos taurus oocytes.Journal of ovarian research · 2020Article
- Purinergic System Signaling in Metainflammation-Associated Osteoarthritis.Frontiers in medicine · 2020Review
- Protective Effect of α-Linolenic Acid on Non-Alcoholic Hepatic Steatosis and Interleukin-6 and -10 in Wistar Rats.Nutrients · 2019Article
- The P2X7 receptor and pannexin-1 are involved in glucose-induced autocrine regulation in β-cells.Scientific reports · 2018Article
- The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study.International journal of ophthalmology · 2018Article
- Resveratrol attenuates type 2 diabetes mellitus by mediating mitochondrial biogenesis and lipid metabolism via Sirtuin type 1.Experimental and therapeutic medicine · 2018Article
- 20-HETE attenuates the response of glucose-stimulated insulin secretion through the AKT/GSK-3β/Glut2 pathway.Endocrine · 2016Article
- Important roles of P2Y receptors in the inflammation and cancer of digestive system.Oncotarget · 2016Review
- PPARα Agonist Fenofibrate Reduced the Secreting Load of β-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance.PPAR research · 2016Article
- Glucose promotes secretion-dependent renal cyst growth.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Article
- Neuroprotection Mediated by P2Y13 Nucleotide Receptors in Neurons.Computational and structural biotechnology journal · 2015Review
- ATP release mechanisms of endothelial cell-mediated stimulus-dependent hyperalgesia.The journal of pain · 2014Article
- Purinergic signalling in endocrine organs.Purinergic signalling · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While high levels of glucose and saturated fatty acids are known to have detrimental effects on beta cell function and survival, the signalling pathways mediating these effects are not entirely known. In a previous study, we found that ADP regulates beta cell insulin secretion and beta cell apoptosis. Using MIN6c4 cells as a model system, we investigated if autocrine/paracrine mechanisms of ADP and purinergic receptors are involved in this process. High glucose (16.7 mmol/l) and palmitate (100 μmol/l) rapidly and potently elevated the extracellular ATP levels, while mannitol was without effect. Both tolbutamide and diazoxide were without effect, while the calcium channel blocker nifedipine, the volume-regulated anion channels (VRAC) inhibitor NPPB, and the pannexin inhibitor carbenoxolone could inhibit both effects. Similarly, silencing the MDR1 gene also blocked nutrient-generated ATP release. These results indicate that calcium channels and VRAC might be involved in the ATP release mechanism. Furthermore, high glucose and palmitate inhibited cAMP production, reduced cell proliferation in MIN6c4 and increased activated Caspase-3 cells in mouse islets and in MIN6c4 cells. The P2Y(13)-specific antagonist MRS2211 antagonized all these effects. Further studies showed that blocking the P2Y(13) receptor resulted in enhanced CREB, Bad and IRS-1 phosphorylation, which are known to be involved in beta cell survival and insulin secretion. These findings provide further support for the concept that P2Y(13) plays an important role in beta cell apoptosis and suggest that autocrine/paracrine mechanisms, related to ADP and P2Y(13) receptors, contribute to glucolipotoxicity.
Indexed as
Identifiers
What Socratic 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 Socratic graph.