ArticleThe Journal of physiology2019
Exendin-4 overcomes cytokine-induced decreases in gap junction coupling via protein kinase A and Epac2 in mouse and human islets.
Article in The Journal of physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 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
- Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell.ACS applied bio materials · 2024Article
- Network representation of multicellular activity in pancreatic islets: Technical considerations for functional connectivity analysis.PLoS computational biology · 2024Article
- Human Beta Cell Functional Adaptation and Dysfunction in Insulin Resistance and Its Reversibility.Nephron · 2024Review
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks.Frontiers in endocrinology · 2023Article
- Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.Frontiers in endocrinology · 2023Article
- Ca2+ Oscillations, Waves, and Networks in Islets From Human Donors With and Without Type 2 Diabetes.Diabetes · 2022Article
- Liraglutide increases islet CaDiabetes, obesity & metabolism · 2022Article
- Is type 2 diabetes mellitus another intercellular junction-related disorder?Experimental biology and medicine (Maywood, N.J.) · 2022Article
- From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science.Frontiers in endocrinology · 2022Review
- Review
- NMDA receptor inhibition increases, synchronizes, and stabilizes the collective pancreatic beta cell activity: Insights through multilayer network analysis.PLoS computational biology · 2021Article
- Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation.Endocrine reviews · 2021Review
- Caloric restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination, and insulin secretion in prediabetic mice.American journal of physiology. Endocrinology and metabolism · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
key pointsThe pancreatic islets of Langerhans maintain glucose homeostasis through insulin secretion, where insulin secretion dynamics are regulated by intracellular Ca ABSTRACT: The pancreatic islets of Langerhans maintain glucose homeostasis. Insulin secretion from islet β-cells is driven by glucose metabolism, depolarization of the cell membrane and an influx of calcium, which initiates the release of insulin. Gap junctions composed of connexin36 (Cx36) electrically couple β-cells, regulating calcium signalling and insulin secretion dynamics. Cx36 coupling is decreased in pre-diabetic mice, suggesting a role for altered coupling in diabetes. Our previous work has shown that pro-inflammatory cytokines decrease Cx36 coupling and that compounds which increase cAMP can increase Cx36 coupling. The goal of this study was to determine if exendin-4, which increases cAMP, can protect against cytokine-induced decreases in Cx36 coupling and altered islet function. In both mouse and human islets, exendin-4 protected against cytokine-induced decreases in coupling and preserved glucose-stimulated calcium signalling. Exendin-4 also protected against protein kinase Cδ-mediated decreases in Cx36 coupling. Exendin-4 preserved coupling in mouse islets by preserving Cx36 levels on the plasma membrane. Exendin-4 regulated Cx36 coupling via both protein kinase A (PKA)- and Epac2-mediated mechanisms in cytokine-treated islets. In mouse islets, modulating Epac2 had a greater impact in mediating Cx36 coupling, while in human islets modulating PKA had a greater impact on Cx36 coupling. Our data indicate that PKA regulates Cx36 coupling through a fast mechanism, such as channel gating, while Epac2 regulates slower mechanisms of regulation, such as Cx36 turnover in the membrane. Increases in Cx36 coupling with exendin-4 may protect against cytokine-mediated β-cell dysfunction to insulin secretion dynamics during the development of diabetes.
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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.