ArticleAmerican journal of physiology. Endocrinology and metabolism2010
PKA-dependent potentiation of glucose-stimulated insulin secretion by Epac activator 8-pCPT-2'-O-Me-cAMP-AM in human islets of Langerhans.
Article in American journal of physiology. Endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- TUDCA and 4-PBA in Preclinical Models of Beta-Cell Secretory Failure: A Systematic Review and Bayesian Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Differential effects of isopropyl alcohol on glucose-induced insulin secretion in INS-1 and MIN6 cells.Pharmacological reports : PR · 2026Article
- A Review of Antidiabetic Medicinal Plants as a Novel Source of Phosphodiesterase Inhibitors: Future Perspective of New Challenges Against Diabetes Mellitus.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive 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
- Mitofusins Mfn1 and Mfn2 Are Required to Preserve Glucose- but Not Incretin-Stimulated β-Cell Connectivity and Insulin Secretion.Diabetes · 2022Article
- Article
- Epac activation ameliorates tubulointerstitial inflammation in diabetic nephropathy.Acta pharmacologica Sinica · 2022Article
- Review
- The Capacity to Secrete Insulin Is Dose-Dependent to Extremely High Glucose Concentrations: A Key Role for Adenylyl Cyclase.Metabolites · 2021Article
- Article
- Glucose Signaling Is Connected to Chromosome Segregation Through Protein Kinase A Phosphorylation of the Dam1 Kinetochore Subunit inGenetics · 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
- Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Chimeric peptide EP45 as a dual agonist at GLP-1 and NPY2R receptors.Scientific reports · 2018Article
- Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets.Bioorganic & medicinal chemistry letters · 2017Review
- Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion.Scientific reports · 2017Article
- Modeling analysis of inositol 1,4,5-trisphosphate receptor-mediated Ca2+ mobilization under the control of glucagon-like peptide-1 in mouse pancreatic β-cells.American journal of physiology. Cell physiology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Potential insulin secretagogue properties of an acetoxymethyl ester of a cAMP analog (8-pCPT-2'-O-Me-cAMP-AM) that activates the guanine nucleotide exchange factors Epac1 and Epac2 were assessed using isolated human islets of Langerhans. RT-QPCR demonstrated that the predominant variant of Epac expressed in human islets was Epac2, although Epac1 was detectable. Under conditions of islet perifusion, 8-pCPT-2'-O-Me-cAMP-AM (10 microM) potentiated first- and second-phase 10 mM glucose-stimulated insulin secretion (GSIS) while failing to influence insulin secretion measured in the presence of 3 mM glucose. The insulin secretagogue action of 8-pCPT-2'-O-Me-cAMP-AM was associated with depolarization and an increase of [Ca(2+)](i) that reflected both Ca(2+) influx and intracellular Ca(2+) mobilization in islet beta-cells. As expected for an Epac-selective cAMP analog, 8-pCPT-2'-O-Me-cAMP-AM (10 microM) failed to stimulate phosphorylation of PKA substrates CREB and Kemptide in human islets. Furthermore, 8-pCPT-2'-O-Me-cAMP-AM (10 microM) had no significant ability to activate AKAR3, a PKA-regulated biosensor expressed in human islet cells by viral transduction. Unexpectedly, treatment of human islets with an inhibitor of PKA activity (H-89) or treatment with a cAMP antagonist that blocks PKA activation (Rp-8-CPT-cAMPS) nearly abolished the action of 8-pCPT-2'-O-Me-cAMP-AM to potentiate GSIS. It is concluded that there exists a permissive role for PKA activity in support of human islet insulin secretion that is both glucose dependent and Epac regulated. This permissive action of PKA may be operative at the insulin secretory granule recruitment, priming, and/or postpriming steps of Ca(2+)-dependent exocytosis.
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.