ArticleThe Journal of clinical investigation2015
Calcium release channel RyR2 regulates insulin release and glucose homeostasis.
Article in The Journal of clinical investigation, 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 125 papers, 3 of them syntheses that pooled it.
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Who cites it
125 citing papers in PubMed, 3 syntheses or guidelines pooled it, 15 citations in OpenAlex.
- Pooled it
- The association of serum magnesium and mortality outcomes in heart failure patients: A systematic review and meta-analysis.Medicine · 2016Pooled it
- Relationship Between Myo-Inositol Supplementary and Gestational Diabetes Mellitus: A Meta-Analysis.Medicine · 2015Pooled it
- Influence of Dapagliflozin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.Journal of diabetes research · 2016Trial
- Transient receptor potential canonical (TRPC) channels in diabetes and associated complications.Channels (Austin, Tex.) · 2026Review
- Cytochrome P450 1a (CYP1A)-Knockout Javanese Medaka Fish Exhibit Diabetic Traits and Reduced Reproductive Capacity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Mitochondrial Homeostasis in Pancreatic β Cell Function: Mechanisms and Therapeutic Targets for Diabetes.Journal of diabetes · 2026Review
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- Extrachromosomal Circular DNA and Transposable Elements in Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Molecular Imprints of Clinical Comorbidities in Hypothalamic Extracellular Vesicles at the Onset of Obesity.ACS omega · 2025Article
- Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes.Cells · 2025Review
- Genetics, manifestations, and management of catecholaminergic polymorphic ventricular tachycardia.Current opinion in cardiology · 2025Review
- NRF2 deficiency leads to inadequate beta cell adaptation during pregnancy and gestational diabetes.Redox biology · 2025Article
- Metabolic-stress-induced mitochondrial calcium dysregulation: a central hub in diabetic cardiomyopathy pathogenesis and treatment.Frontiers in endocrinology · 2025Review
- Multi-omics landscape of childhood simple obesity: novel insights into pathogenesis and biomarkers discovery.Cell & bioscience · 2024Article
- Mechanistic role of mesencephalic astrocyte-derived neurotrophic factor in myocardial ischemia/reperfusion injury.Molecular medicine (Cambridge, Mass.) · 2024Article
- Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning.Biomedicines · 2024Article
- Spatiotemporal orchestration of calcium-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop.PLoS computational biology · 2024Article
- Selection and Regulatory Network Analysis of Differential CircRNAs in the Hypothalamus of Goats with High and Low Reproductive Capacity.International journal of molecular sciences · 2024Article
- Purinergic agonists increase [CaAmerican journal of physiology. Cell physiology · 2024Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 6 institutions in 6 countries.
Funding
Abstract
The type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic reticulum (ER) of several types of cells, including cardiomyocytes and pancreatic β cells. In cardiomyocytes, RyR2-dependent Ca2+ release is critical for excitation-contraction coupling; however, a functional role for RyR2 in β cell insulin secretion and diabetes mellitus remains controversial. Here, we took advantage of rare RyR2 mutations that were identified in patients with a genetic form of exercise-induced sudden death (catecholaminergic polymorphic ventricular tachycardia [CPVT]). As these mutations result in a "leaky" RyR2 channel, we exploited them to assess RyR2 channel function in β cell dynamics. We discovered that CPVT patients with mutant leaky RyR2 present with glucose intolerance, which was heretofore unappreciated. In mice, transgenic expression of CPVT-associated RyR2 resulted in impaired glucose homeostasis, and an in-depth evaluation of pancreatic islets and β cells from these animals revealed intracellular Ca2+ leak via oxidized and nitrosylated RyR2 channels, activated ER stress response, mitochondrial dysfunction, and decreased fuel-stimulated insulin release. Additionally, we verified the effects of the pharmacological inhibition of intracellular Ca2+ leak in CPVT-associated RyR2-expressing mice, in human islets from diabetic patients, and in an established murine model of type 2 diabetes mellitus. Taken together, our data indicate that RyR2 channels play a crucial role in the regulation of insulin secretion and glucose homeostasis.
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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 OpenQuestion graph.