ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2023
Advanced Glycation End Products Downregulate Connexin 43 and Connexin 40 in Diabetic Atrial Myocytes via the AMPK Pathway.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Review
- Complex interrelationship and therapeutic advances in diabetic patients with atrial fibrillation.World journal of cardiology · 2025Review
- Connexin 40 in atrial fibrillation: pathophysiological roles and regulatory mechanisms.Annals of medicine · 2025Review
- Metabolic Remodeling and Mitochondrial Stress in Atrial Fibrillation: Mechanisms and Translational Targets.Reviews in cardiovascular medicine · 2025Review
- Atrial Fibrillation in Diabetes: Pathogenesis and Targeted Rhythm Control Strategies.Current issues in molecular biology · 2025Review
- Identifying and establishing the critical elements of a human cardiac in-vitro model for studying type-II diabetes.Discover applied sciences · 2025Article
- Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications.Nature reviews. Cardiology · 2024Review
- Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.Vascular health and risk management · 2024Review
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Authors and funding
14 authors at 2 institutions in 1 country.
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Abstract
Purpose: Diabetes mellitus is an independent risk factor for atrial fibrillation (AF), which may be related to accumulation of advanced glycation end products (AGEs). However, the mechanisms involved are not completely clear. Abnormality of gap junction proteins, especially connexin 43 (Cx43) and connexin 40 (Cx40) in atrial myocytes, is an important cause of increased susceptibility of AF. The aim of our work is to investigate the mechanism of dysregulated Cx43 and Cx40 in atrial myocytes of diabetic rats. Methods: We established a type 1 diabetic rat model by intraperitoneal injection of streptozotocin. HL-1 cells and primary rat atrial myocytes were treated with AGEs in vitro. Using Western blotting, immunofluorescence staining, immunohistochemistry, and lucifer yellow diffusion measurements, we investigated dysregulation of Cx43 and Cx40 and its mechanism in atrial myocytes of diabetic rats. Results: Accumulation of AGEs was found in diabetic rats. The expression of Cx43 and Cx40 was reduced in the atrium of diabetic rats, accompanied by the decrease of phosphorylated Adenosine 5'-monophosphate-activated protein kinase (p-AMPK). Similar results were found in cultured HL-1 cells and primary rat atrial myocytes, suggesting a role of AGEs on gap junction proteins. An AMPK agonist, 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), reversed the down-regulated Cx43 expression induced by AGEs stimulation. More importantly, lucifer yellow diffusion assay showed that AGEs significantly affected gap junctional function, and these changes were reversed by AICAR. Conclusion: Thus, we conclude that AGEs cause dysregulation of Cx43 and Cx40 in diabetic atria via the AMPK pathway, thereby leading to gap junction dysfunction, which may contribute to the increased AF susceptibility in diabetes.
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