ArticleProceedings of the National Academy of Sciences of the United States of America1998
In situ activation of the type 2 ryanodine receptor in pancreatic beta cells requires cAMP-dependent phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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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.
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Who cites it
34 citing papers in PubMed, 108 citations in OpenAlex.
- Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes.Cells · 2025Review
- β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro.Pharmacology research & perspectives · 2025Article
- Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and CaReviews of physiology, biochemistry and pharmacology · 2021Review
- Control by CaCell calcium · 2020Review
- Calcium-induced calcium release in proximity to hair cell BK channels revealed by PKA activation.Physiological reports · 2020Article
- SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity.Diabetes · 2016Article
- Article
- The ryanodine receptor agonist 4-chloro-3-ethylphenol blocks ORAI store-operated channels.British journal of pharmacology · 2014Article
- Ca(2+) channels on the move.Biochemistry · 2009Review
- Aquaporin-2 in the "-omics" era.The Journal of biological chemistry · 2009Review
- Roles of IP3R and RyR Ca2+ channels in endoplasmic reticulum stress and beta-cell death.Diabetes · 2009Article
- Akt and ERK1/2 pathways are components of the vasopressin signaling network in rat native IMCD.American journal of physiology. Renal physiology · 2008Article
- RyR channels and glucose-regulated pancreatic beta-cells.European biophysics journal : EBJ · 2008Article
- Mechanisms of action of glucagon-like peptide 1 in the pancreas.Pharmacology & therapeutics · 2007Review
- Pathway-specific effect of caffeine on protection against UV irradiation-induced apoptosis in corneal epithelial cells.Investigative ophthalmology & visual science · 2007Article
- A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells.The Journal of physiology · 2005Article
- Atypical Ca2+-induced Ca2+ release from a sarco-endoplasmic reticulum Ca2+-ATPase 3-dependent Ca2+ pool in mouse pancreatic beta-cells.The Journal of physiology · 2004Article
- Review
- Cyclic nucleotide phosphodiesterases in pancreatic islets.Diabetologia · 2003Review
- Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells.The Biochemical journal · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Molecular mechanisms that regulate in situ activation of ryanodine receptors (RY) in different cells are poorly understood. Here we demonstrate that caffeine (10 mM) released Ca2+ from the endoplasmic reticulum (ER) in the form of small spikes in only 14% of cultured fura-2 loaded beta cells from ob/ob mice. Surprisingly, when forskolin, an activator of adenylyl cyclase was present, caffeine induced larger Ca2+ spikes in as many as 60% of the cells. Forskolin or the phosphodiesterase-resistant PKA activator Sp-cAMPS alone did not release Ca2+ from ER. 4-Chloro-3-ethylphenol (4-CEP), an agent that activates RYs in other cell systems, released Ca2+ from ER, giving rise to a slow and small increase in [Ca2+]i in beta cells. Prior exposure of cells to forskolin or caffeine (5 mM) qualitatively altered Ca2+ release by 4-CEP, giving rise to Ca2+ spikes. In glucose-stimulated beta cells forskolin induced Ca2+ spikes that were enhanced by 3,9-dimethylxanthine, an activator of RYs. Analysis of RNA from islets and insulin-secreting betaTC-3-cells by RNase protection assay, using type-specific RY probes, revealed low-level expression of mRNA for the type 2 isoform of the receptor (RY2). We conclude that in situ activation of RY2 in beta cells requires cAMP-dependent phosphorylation, a process that recruits the receptor in a functionally operative form.
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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.