ArticleThe Journal of physiology2001
cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic beta-cells.
Article in The Journal of physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 205 citations in OpenAlex.
- LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.Molecular metabolism · 2018 · on this mapTrial
- Flavonoids of Mao Jian Green Tea Ameliorate Glycemic Metabolism in Type-2-Diabetic Rats via AMPK Signaling Pathways and Gut Microbiota Regulation.Foods (Basel, Switzerland) · 2025Article
- Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes.Cells · 2025Review
- Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- GLP-1 receptor agonists and gallbladder disease risk: insights into molecular mechanisms and clinical implications.Therapeutic advances in endocrinology and metabolism · 2025Review
- Class B1 GPCRs: insights into multireceptor pharmacology for the treatment of metabolic disease.American journal of physiology. Endocrinology and metabolism · 2024Review
- Pancreatic beta-cell mass and function and therapeutic implications of using antidiabetic medications in type 2 diabetes.Journal of diabetes investigation · 2024Review
- GLP-1R Signaling and Functional Molecules in Incretin Therapy.Molecules (Basel, Switzerland) · 2023Review
- The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks.Frontiers in endocrinology · 2023Article
- Liraglutide increases islet CaDiabetes, obesity & metabolism · 2022Article
- Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and CaiScience · 2022Article
- Review
- Review
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- S1P Signaling Pathways in Pathogenesis of Type 2 Diabetes.Journal of diabetes research · 2021Article
- Lorcaserin Inhibit Glucose-Stimulated Insulin Secretion and Calcium Influx in Murine Pancreatic Islets.Frontiers in pharmacology · 2021Article
- The Interplay of Glucagon-Like Peptide-1 Receptor Trafficking and Signalling in Pancreatic Beta Cells.Frontiers in endocrinology · 2021Review
- Article
- ATP-sensitive KPflugers Archiv : European journal of physiology · 2019Article
- Glucagon-like peptide 1 (GLP-1).Molecular metabolism · 2019 · on this mapReview
34 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
1. The signal transduction pathway responsible for cAMP-dependent Ca2+-induced Ca2+ release (CICR) from endoplasmic reticulum Ca2+ stores was assessed in the insulin-secreting cell line INS-1. 2. CICR was triggered by the GLP-1 receptor agonist exendin-4, an effect mimicked by caffeine, Sp-cAMPS or forskolin. CICR required influx of Ca2+ through L-type voltage-dependent Ca2+ channels, and was blocked by treatment with nimodipine, thapsigargin, or ryanodine, but not by the IP3 receptor antagonist xestospongin C. 3. Treatment with the cAMP antagonist 8-Br-Rp-cAMPS blocked CICR in response to exendin-4, whereas the PKA inhibitor H-89 was ineffective when tested at a concentration demonstrated to inhibit PKA-dependent gene expression. 4. RT-PCR of INS-1 cells demonstrated expression of mRNA coding for the type-II isoform of cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF-II, Epac2). 5. CICR in response to forskolin was blocked by transient transfection and expression of a dominant negative mutant isoform of cAMP-GEF-II in which inactivating mutations were introduced into the exchange factor's two cAMP-binding domains. 6. It is concluded that CICR in INS-1 cells results from GLP-1 receptor-mediated sensitization of the intracellular Ca2+ release mechanism, a signal transduction pathway independent of PKA, but which requires cAMP-GEF-II.
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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.