Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes

Ryanodine receptors (RyRs) are large intracellular Ca2+ release channels primarily found in muscle and nerve cells and also present at low levels in pancreatic islet endocrine cells. This review examines the role of RyRs in islet cell function, focusing on calcium signaling and hormone secretion, wh...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Vol. 14; no. 10; p. 690
Main Author: Islam, Md. Shahidul
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 10.05.2025
MDPI
Subjects:
Agonists
Animals
Apoptosis
Beta cells
beta-cell electrical activity and ryanodine receptors
Caffeine
Calcium (intracellular)
Calcium (reticular)
Calcium - metabolism
Calcium channels
Calcium release channels
Calcium Signaling
calcium signaling in beta cells
Calcium signalling
calcium-induced calcium release in islet cells
Delta cells
Dextrose
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus - metabolism
Diabetes Mellitus, Type 2 - metabolism
Endoplasmic reticulum
endoplasmic reticulum stress in beta cells
Enzymes
Experiments
Glucagon
Glucagon-like peptide 1
glucagon-like peptide-1 and ryanodine receptors
Glucose
Hormones - metabolism
Humans
Insulin
Insulin Secretion
Insulin-Secreting Cells - metabolism
Intracellular signalling
Islet cells
Islets of Langerhans - metabolism
Isoforms
Neurons
Pathogenesis
Phosphorylation
Receptor mechanisms
Review
Ryanodine Receptor Calcium Release Channel - metabolism
Ryanodine receptors
ryanodine receptors and diabetes
ryanodine receptors and insulin secretion
ryanodine receptors and store-operated calcium entry
ryanodine receptors in delta cells
ryanodine receptors in islets cells
Type 2 diabetes
ryanodine receptors in delta cells
ryanodine receptors and diabetes
endoplasmic reticulum stress in beta cells
ryanodine receptors and store-operated calcium entry
beta-cell electrical activity and ryanodine receptors
calcium signaling in beta cells
calcium-induced calcium release in islet cells
glucagon-like peptide-1 and ryanodine receptors
ryanodine receptors in islets cells
ryanodine receptors and insulin secretion
ISSN:2073-4409, 2073-4409
Online Access:Get full text
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Summary:Ryanodine receptors (RyRs) are large intracellular Ca2+ release channels primarily found in muscle and nerve cells and also present at low levels in pancreatic islet endocrine cells. This review examines the role of RyRs in islet cell function, focusing on calcium signaling and hormone secretion, while addressing the ongoing debate regarding their significance due to their limited expression. We explore conflicting experimental results and their potential causes, synthesizing current knowledge on RyR isoforms in islet cells, particularly in beta and delta cells. The review discusses how RyR-mediated calcium-induced calcium release enhances, rather than drives, glucose-stimulated insulin secretion. We examine the phosphorylation-dependent regulation of beta-cell RyRs, the concept of “leaky ryanodine receptors”, and the roles of RyRs in endoplasmic reticulum stress, apoptosis, store-operated calcium entry, and beta-cell electrical activity. The relationship between RyR dysfunction and the development of impaired insulin secretion in diabetes is assessed, noting their limited role in human diabetes pathogenesis given the disease’s polygenic nature. We highlight the established role of RyR-mediated CICR in the mechanism of action of common type 2 diabetes treatments, such as glucagon-like peptide-1, which enhances insulin secretion. By integrating findings from electrophysiological, molecular, and clinical studies, this review provides a balanced perspective on RyRs in islet cell physiology and pathology, emphasizing their significance in both normal insulin secretion and current diabetes therapies.
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ISSN:2073-4409
2073-4409
DOI:10.3390/cells14100690