ArticleCell death and differentiation2013
Connexin36 contributes to INS-1E cells survival through modulation of cytokine-induced oxidative stress, ER stress and AMPK activity.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Connexins in metabolic control: linking brain cellular communication to systemic homeostasis.Life medicine · 2026Review
- Connexin Regulation and Modulation of Neural Stem Cell Differentiation Induced by Cell-Permeable Itaconate.Journal of cellular physiology · 2026Article
- Protector Role of Cx30.2 in Pancreatic β-Cell against Glucotoxicity-Induced Apoptosis.Biology · 2024Article
- Alpha4 contributes to the dysfunction of the pancreatic beta cell under metabolic stress.Molecular and cellular endocrinology · 2022Article
- Inhibition of Connexin 36 attenuates HMGB1-mediated depressive-like behaviors induced by chronic unpredictable mild stress.Brain and behavior · 2022Article
- Modulation of Gap Junction Coupling Within the Islet of Langerhans During the Development of Type 1 Diabetes.Frontiers in physiology · 2022Article
- The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress.PloS one · 2022Article
- The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on [Formula: see text] dynamics.Scientific reports · 2021Article
- The Ameliorating Effects of Bushen Huatan Granules and Kunling Wan on Polycystic Ovary Syndrome Induced by Dehydroepiandrosterone in Rats.Frontiers in physiology · 2021Article
- Exendin-4 overcomes cytokine-induced decreases in gap junction coupling via protein kinase A and Epac2 in mouse and human islets.The Journal of physiology · 2019Article
- Dysfunctional autophagy following exposure to pro-inflammatory cytokines contributes to pancreatic β-cell apoptosis.Cell death & disease · 2018Article
- Monitoring p53 by MDM2 and MDMX is required for endocrine pancreas development and function in a spatio-temporal manner.Developmental biology · 2017Article
- microRNA-802 is involved in palmitate-induced damage to pancreatic β cells through repression of sirtuin 6.International journal of clinical and experimental pathology · 2017Article
- Junctophilin 3 expresses in pancreatic beta cells and is required for glucose-stimulated insulin secretion.Cell death & disease · 2016Article
- Adaptation of pancreatic islet cyto-architecture during development.Physical biology · 2016Article
- Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ.The Journal of biological chemistry · 2016Article
- Glibenclamide Prevents Diabetes in NOD Mice.PloS one · 2016Article
- A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells.PloS one · 2016Article
- Can exposure to environmental chemicals increase the risk of diabetes type 1 development?BioMed research international · 2015Review
- New insights into the role of connexins in pancreatic islet function and diabetes.FEBS letters · 2014Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Cell-to-cell communication mediated by gap junctions made of Connexin36 (Cx36) contributes to pancreatic β-cell function. We have recently demonstrated that Cx36 also supports β-cell survival by a still unclear mechanism. Using specific Cx36 siRNAs or adenoviral vectors, we now show that Cx36 downregulation promotes apoptosis in INS-1E cells exposed to the pro-inflammatory cytokines (IL-1β, TNF-α and IFN-γ) involved at the onset of type 1 diabetes, whereas Cx36 overexpression protects against this effect. Cx36 overexpression also protects INS-1E cells against endoplasmic reticulum (ER) stress-mediated apoptosis, and alleviates the cytokine-induced production of reactive oxygen species, the depletion of the ER Ca(2+) stores, the CHOP overexpression and the degradation of the anti-apoptotic protein Bcl-2 and Mcl-1. We further show that cytokines activate the AMP-dependent protein kinase (AMPK) in a NO-dependent and ER-stress-dependent manner and that AMPK inhibits Cx36 expression. Altogether, the data suggest that Cx36 is involved in Ca(2+) homeostasis within the ER and that Cx36 expression is downregulated following ER stress and subsequent AMPK activation. As a result, cytokine-induced Cx36 downregulation elicits a positive feedback loop that amplifies ER stress and AMPK activation, leading to further Cx36 downregulation. The data reveal that Cx36 plays a central role in the oxidative stress and ER stress induced by cytokines and the subsequent regulation of AMPK activity, which in turn controls Cx36 expression and mitochondria-dependent apoptosis of insulin-producing cells.
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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.