ArticleDiabetes2013
Pancreatic β-cell response to increased metabolic demand and to pharmacologic secretagogues requires EPAC2A.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Vitamin K as an Endocrine Modulator: Mechanistic Links to Glucose Metabolism and Beyond.Nutrients · 2026Review
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks.Frontiers in endocrinology · 2023Article
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- The therapeutic potential of GLP-1 receptor biased agonism.British journal of pharmacology · 2022 · on this mapReview
- Molecular pathways dysregulated by PbToxicology research · 2022Article
- 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
- Positively selected genes in the hoary bat (PeerJ · 2022Article
- Engineering islets from stem cells for advanced therapies of diabetes.Nature reviews. Drug discovery · 2021Review
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- Mice depleted for Exchange Proteins Directly Activated by cAMP (Epac) exhibit irregular liver regeneration in response to partial hepatectomy.Scientific reports · 2019Article
- Gonadotrope androgen receptor mediates pituitary responsiveness to hormones and androgen-induced subfertility.JCI insight · 2019Article
- Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP.Scientific reports · 2017Article
- Sucralose activates an ERK1/2-ribosomal protein S6 signaling axis.FEBS open bio · 2017Article
- β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions.Nature communications · 2017Article
- Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.International journal of obesity (2005) · 2017Article
- Article
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5 authors at 2 institutions in 1 country.
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Abstract
Incretin hormone action on β-cells stimulates in parallel two different intracellular cyclic AMP-dependent signaling branches mediated by protein kinase A and exchange protein activated by cAMP islet/brain isoform 2A (EPAC2A). Both pathways contribute toward potentiation of glucose-stimulated insulin secretion (GSIS). However, the overall functional role of EPAC2A in β-cells as it relates to in vivo glucose homeostasis remains incompletely understood. Therefore, we have examined in vivo GSIS in global EPAC2A knockout mice. Additionally, we have conducted in vitro studies of GSIS and calcium dynamics in isolated EPAC2A-deficient islets. EPAC2A deficiency does not impact GSIS in mice under basal conditions. However, when mice are exposed to diet-induced insulin resistance, pharmacologic secretagogue stimulation of β-cells with an incretin hormone glucagon-like peptide-1 analog or with a fatty acid receptor 1/G protein-coupled receptor 40 selective activator, EPAC2A is required for the increased β-cell response to secretory demand. Under these circumstances, EPAC2A is required for potentiating the early dynamic increase in islet calcium levels after glucose stimulation, which is reflected in potentiated first-phase insulin secretion. These studies broaden our understanding of EPAC2A function and highlight its significance during increased secretory demand or drive on β-cells. Our findings advance the rationale for developing EPAC2A-selective pharmacologic activators for β-cell-targeted pharmacotherapy in type 2 diabetes.
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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.