ArticleThe Journal of physiology2010
Epac2-dependent mobilization of intracellular Ca²+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in β-cells of phospholipase C-ε knockout mice.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 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
40 citing papers in PubMed, 69 citations in OpenAlex.
- Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026Review
- Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes.Cells · 2025Review
- Phospholipase C-ε defines a PACAP-stimulated pathway for secretion in the chromaffin cell.Journal of neuroendocrinology · 2023Article
- A unique melanocortin-4-receptor signaling profile for obesity-associated constitutively active variants.Journal of molecular endocrinology · 2023Article
- PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells.The Journal of general physiology · 2023Article
- Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.Frontiers in endocrinology · 2023Article
- The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks.Frontiers in endocrinology · 2023Article
- The therapeutic potential of GLP-1 receptor biased agonism.British journal of pharmacology · 2022 · on this mapReview
- Intra-islet glucagon confers β-cell glucose competence for first-phase insulin secretion and favors GLP-1R stimulation by exogenous glucagon.The Journal of biological chemistry · 2022Article
- Review
- Review
- The sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid is a glucose-dependent potentiator of insulin secretion.Scientific reports · 2020Article
- Article
- Cyclic AMP links glucose stimulation to somatostatin secretion in δ-cells.The Journal of general physiology · 2019Article
- Glucose stimulates somatostatin secretion in pancreatic δ-cells by cAMP-dependent intracellular CaThe Journal of general physiology · 2019Article
- Sodium current inhibition following stimulation of exchange protein directly activated by cyclic-3',5'-adenosine monophosphate (Epac) in murine skeletal muscle.Scientific reports · 2019Article
- Reduced Expression ofFrontiers in endocrinology · 2019Article
- Regulation of cAMP accumulation and activity by distinct phosphodiesterase subtypes in INS-1 cells and human pancreatic β-cells.PloS one · 2019Article
- PLCε signaling in cancer.Journal of cancer research and clinical oncology · 2016Review
- Pancreatic regulation of glucose homeostasis.Experimental & molecular medicine · 2016Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Calcium can be mobilized in pancreatic β-cells via a mechanism of Ca(2+)-induced Ca(2+) release (CICR), and cAMP-elevating agents such as exendin-4 facilitate CICR in β-cells by activating both protein kinase A and Epac2. Here we provide the first report that a novel phosphoinositide-specific phospholipase C- (PLC-) is expressed in the islets of Langerhans, and that the knockout (KO) of PLC- gene expression in mice disrupts the action of exendin-4 to facilitate CICR in the β-cells of these mice. Thus, in the present study, in which wild-type (WT) C57BL/6 mouse β-cells were loaded with the photolabile Ca(2+) chelator NP-EGTA, the UV flash photolysis-catalysed uncaging of Ca(2+) generated CICR in only 9% of the β-cells tested, whereas CICR was generated in 82% of the β-cells pretreated with exendin-4. This action of exendin-4 to facilitate CICR was reproduced by cAMP analogues that activate protein kinase A (6-Bnz-cAMP-AM) or Epac2 (8-pCPT-2'-O-Me-cAMP-AM) selectively. However, in β-cells of PLC- KO mice, and also Epac2 KO mice, these test substances exhibited differential efficacies in the CICR assay such that exendin-4 was partly effective, 6-Bnz-cAMP-AM was fully effective, and 8-pCPT-2'-O-Me-cAMP-AM was without significant effect. Importantly, transduction of PLC- KO β-cells with recombinant PLC- rescued the action of 8-pCPT-2'-O-Me-cAMP-AM to facilitate CICR, whereas a K2150E PLC- with a mutated Ras association (RA) domain, or a H1640L PLC- that is catalytically dead, were both ineffective. Since 8-pCPT-2'-O-Me-cAMP-AM failed to facilitate CICR in WT β-cells transduced with a GTPase activating protein (RapGAP) that downregulates Rap activity, the available evidence indicates that a signal transduction 'module' comprised of Epac2, Rap and PLC- exists in β-cells, and that the activities of Epac2 and PLC- are key determinants of CICR in this cell type.
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.