ArticleThe Journal of biological chemistry2016
Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ.
Article in The Journal of biological chemistry, 2016. 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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34 citing papers in PubMed, 56 citations in OpenAlex.
- Diminished gap junction coupling under diabetogenic conditions does not drive loss of functional β-cell subpopulations.The Journal of general physiology · 2026Article
- Isolated Pancreatic Islet Treatment and Apoptosis Measurement.Journal of visualized experiments : JoVE · 2025Article
- Stressed β-cells contribute to loss of peri-islet extracellular matrix in type 1 diabetes.Frontiers in endocrinology · 2025Article
- Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes.Nature metabolism · 2024Article
- Exploring pancreatic beta-cell subgroups and their connectivity.Nature metabolism · 2024Review
- Extracellular matrix stiffness mediates insulin secretion in pancreatic islets via mechanosensitive Piezo1 channel regulated CaMatrix biology plus · 2024Article
- Human Beta Cell Functional Adaptation and Dysfunction in Insulin Resistance and Its Reversibility.Nephron · 2024Review
- Article
- Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.PLoS computational biology · 2023Article
- Restoring connexin-36 function in diabetogenic environments precludes mouse and human islet dysfunction.The Journal of physiology · 2023Article
- Ca2+ Oscillations, Waves, and Networks in Islets From Human Donors With and Without Type 2 Diabetes.Diabetes · 2022Article
- Is type 2 diabetes mellitus another intercellular junction-related disorder?Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Dynamic changes in β-cell [CaMolecular metabolism · 2022Article
- Mechanisms of Immunomodulation and Cytoprotection Conferred to Pancreatic Islet by Human Amniotic Epithelial Cells.Stem cell reviews and reports · 2022Article
- Modulation of Gap Junction Coupling Within the Islet of Langerhans During the Development of Type 1 Diabetes.Frontiers in physiology · 2022Article
- Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation.Metallomics : integrated biometal science · 2021Article
- The mutual interplay of redox signaling and connexins.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Review
- The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on [Formula: see text] dynamics.Scientific reports · 2021Article
- NMDA receptor inhibition increases, synchronizes, and stabilizes the collective pancreatic beta cell activity: Insights through multilayer network analysis.PLoS computational biology · 2021Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKCδ, we aimed to understand the role of PKCδ in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF-α, IL-1β, and IFN-γ. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKCδ and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKCδ, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes.
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