ArticlePloS one2015
Glucose-Dependent Insulin Secretion in Pancreatic β-Cell Islets from Male Rats Requires Ca2+ Release via ROS-Stimulated Ryanodine Receptors.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
- A mitochondrial ROS-dependent antiviral response promotes β cell resilience and is diminished in donors with type 1 diabetes.Science translational medicine · 2026Article
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- The antioxidant, N-acetyl-L-cysteine, affects beta cell oxidative stress, insulin secretion, and intracellular signaling pathways in MIN6 cells.Cell and tissue research · 2025Article
- Expression, localization and regulation of NADPH oxidases in pancreatic beta cells.Redox report : communications in free radical research · 2025Article
- Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes.Cells · 2025Review
- IFN-α Induces Heterogenous ROS Production in Human β-Cells.bioRxiv : the preprint server for biology · 2025Article
- Single Low-Dose Ionizing Radiation Transiently Enhances Rat RIN-m5F Cell Function via the ROS/p38 MAPK Pathway Without Inducing Cell Damage.Antioxidants (Basel, Switzerland) · 2025Article
- Exploring the key role of DNA methylation as an epigenetic modulator in oxidative stress related islet cell injury in patients with type 2 diabetes mellitus: a review.Journal of diabetes and metabolic disorders · 2024Review
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression.International journal of molecular sciences · 2024Review
- Selenium Nanodots (SENDs) as Antioxidants and Antioxidant-Prodrugs to Rescue Islet β Cells in Type 2 Diabetes Mellitus by Restoring Mitophagy and Alleviating Endoplasmic Reticulum Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- High-resolution analysis of the cytosolic CaAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Uncoupling protein 2 and aldolase B impact insulin release by modulating mitochondrial function and CaiScience · 2022Article
- The manifold roles of protein S-nitrosylation in the life of insulin.Nature reviews. Endocrinology · 2022Review
- Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management.Frontiers in endocrinology · 2022Review
- Glucose-activatable insulin delivery with charge-conversional polyelectrolyte multilayers for diabetes care.Frontiers in bioengineering and biotechnology · 2022Article
- Research progress on the mechanism of beta-cell apoptosis in type 2 diabetes mellitus.Frontiers in endocrinology · 2022Review
- Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells requires an increase in intracellular free Ca2+ concentration ([Ca2+]). Glucose uptake into β-cells promotes Ca2+ influx and reactive oxygen species (ROS) generation. In other cell types, Ca2+ and ROS jointly induce Ca2+ release mediated by ryanodine receptor (RyR) channels. Therefore, we explored here if RyR-mediated Ca2+ release contributes to GSIS in β-cell islets isolated from male rats. Stimulatory glucose increased islet insulin secretion, and promoted ROS generation in islets and dissociated β-cells. Conventional PCR assays and immunostaining confirmed that β-cells express RyR2, the cardiac RyR isoform. Extended incubation of β-cell islets with inhibitory ryanodine suppressed GSIS; so did the antioxidant N-acetyl cysteine (NAC), which also decreased insulin secretion induced by glucose plus caffeine. Inhibitory ryanodine or NAC did not affect insulin secretion induced by glucose plus carbachol, which engages inositol 1,4,5-trisphosphate receptors. Incubation of islets with H2O2 in basal glucose increased insulin secretion 2-fold. Inhibitory ryanodine significantly decreased H2O2-stimulated insulin secretion and prevented the 4.5-fold increase of cytoplasmic [Ca2+] produced by incubation of dissociated β-cells with H2O2. Addition of stimulatory glucose or H2O2 (in basal glucose) to β-cells disaggregated from islets increased RyR2 S-glutathionylation to similar levels, measured by a proximity ligation assay; in contrast, NAC significantly reduced the RyR2 S-glutathionylation increase produced by stimulatory glucose. We propose that RyR2-mediated Ca2+ release, induced by the concomitant increases in [Ca2+] and ROS produced by stimulatory glucose, is an essential step in GSIS.
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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.