ArticleEndocrinology2014
Activators of PKA and Epac distinctly influence insulin secretion and cytosolic Ca2+ in female mouse islets stimulated by glucose and tolbutamide.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- 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
- 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
- βLung · 2021Article
- Glycine Release Is Potentiated by cAMP via EPAC2 and CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Review
- The Capacity to Secrete Insulin Is Dose-Dependent to Extremely High Glucose Concentrations: A Key Role for Adenylyl Cyclase.Metabolites · 2021Article
- Lorcaserin Inhibit Glucose-Stimulated Insulin Secretion and Calcium Influx in Murine Pancreatic Islets.Frontiers in pharmacology · 2021Article
- Article
- The functional impact of G protein-coupled receptor 142 (Gpr142) on pancreatic β-cell in rodent.Pflugers Archiv : European journal of physiology · 2019Article
- Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Exendin-4 overcomes cytokine-induced decreases in gap junction coupling via protein kinase A and Epac2 in mouse and human islets.The Journal of physiology · 2019Article
- Role of cAMP and phosphodiesterase signaling in liver health and disease.Cellular signalling · 2018Review
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- Sucralose activates an ERK1/2-ribosomal protein S6 signaling axis.FEBS open bio · 2017Article
- Gene Editing, Gene Therapy, and Cell Xenotransplantation: Cell Transplantation Across Species.Current transplantation reports · 2017Review
- Rp-cAMPS Prodrugs Reveal the cAMP Dependence of First-Phase Glucose-Stimulated Insulin Secretion.Molecular endocrinology (Baltimore, Md.) · 2015Article
- The future of EPAC-targeted therapies: agonism versus antagonism.Trends in pharmacological sciences · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amplification of insulin secretion by cAMP is mediated by protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). Using selective activators, we determined how each effector influences the cytosolic free Ca(2+) concentration ([Ca(2+)]c) and insulin secretion in mouse islets. Alone PKA activator amplified glucose- and tolbutamide-induced insulin secretion, with a greater impact on second than first phase. Epac activator strongly amplified both phases in response to either secretagogue. Amplification was even greater when activators were combined. Although both activators similarly amplified glucose-induced insulin secretion, Epac activator was particularly efficient on tolbutamide-induced insulin secretion. That greater efficacy is attributed to higher [Ca(2+)]c rather than interaction of tolbutamide with Epac, because it was also observed during KCl stimulation. Moreover, in contrast to Epac activator, tolbutamide was inactive when insulin secretion was increased by gliclazide, and its effect on glucose-induced insulin secretion was unaffected by an inhibitor of Epac2. PKA activator increased [Ca(2+)]c during acute or steady-state glucose stimulation, whereas Epac activator had no effect alone or in combination. Neither activator affected [Ca(2+)]c response to tolbutamide or KCl. Metabolic (glucose-mediated) amplification of insulin secretion was unaffected by PKA activator. It was attenuated when insulin secretion was augmented by Epac activator but insensitive to Epac2 inhibitor, which suggests distinct although somewhat overlapping mechanisms. In conclusion, activators of PKA and Epac amplify insulin secretion by augmenting the action of Ca(2+) on exocytosis and, for PKA only, slightly increasing glucose-induced [Ca(2+)]c rise. The influence of Epac seems more important than that of PKA during first phase.
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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.