ArticleBMC cardiovascular disorders2018
Metformin regulates atrial SK2 and SK3 expression through inhibiting the PKC/ERK signaling pathway in type 2 diabetic rats.
Article in BMC cardiovascular disorders, 2018. 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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16 citing papers in PubMed, 27 citations in OpenAlex.
- Metformin and Risk of New-Onset Atrial Fibrillation in Type 2 Diabetes: A Systematic Review and Meta-Analysis.Diagnostics (Basel, Switzerland) · 2025Review
- Role of Protein Kinase C in Metabolic Regulation of Coronary Endothelial Small Conductance Calcium-Activated Potassium Channels.Journal of the American Heart Association · 2024Article
- Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.Vascular health and risk management · 2024Review
- Effects of Electrical Remodeling on Atrial Fibrillation in Diabetes Mellitus.Reviews in cardiovascular medicine · 2023Review
- Dendritic cell-mediated chronic low-grade inflammation is regulated by the RAGE-TLR4-PKCβMolecular medicine (Cambridge, Mass.) · 2022Article
- Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.Frontiers in physiology · 2022Article
- MicroRNA miR-126 attenuates brain injury in septic rats via NF-κB signaling pathway.Bioengineered · 2021Article
- Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway.International immunopharmacology · 2021Article
- Metformin attenuates diabetic renal injury via the AMPK-autophagy axis.Experimental and therapeutic medicine · 2021Article
- Metformin Is Associated With a Lower Risk of Atrial Fibrillation and Ventricular Arrhythmias Compared With Sulfonylureas: An Observational Study.Circulation. Arrhythmia and electrophysiology · 2021Observational
- Lidocaine attenuates CFA-induced inflammatory pain in rats by regulating the MAPK/ERK/NF-κB signaling pathway.Experimental and therapeutic medicine · 2021Article
- The regulation of the small-conductance calcium-activated potassium current and the mechanisms of sex dimorphism in J wave syndrome.Pflugers Archiv : European journal of physiology · 2021Review
- Mogroside IIe Ameliorates Cardiomyopathy by Suppressing Cardiomyocyte Apoptosis in a Type 2 Diabetic Model.Frontiers in pharmacology · 2021Article
- Signalling pathways implicated in the pathogenesis of rheumatic heart disease (Review).Experimental and therapeutic medicine · 2021Review
- Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-κB AxisBalkan medical journal · 2020Article
- Urinary Bladder Weight and Function in a Rat Model of Mild Hyperglycemia and Its Treatment With Dapagliflozin.Frontiers in pharmacology · 2019Article
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6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOur previous study showed that metformin regulates the mRNA and protein levels of type 2 small conductance calcium-activated potassium channel (SK2) and type 3 small conductance calcium-activated potassium channels (SK3) in atrial tissue as well as the ion current of atrial myocytes in rats with type 2 diabetes mellitus (T2DM), but the underlying signaling mechanism is unknown. This study aimed to investigate whether metformin regulates atrial SK2 and SK3 protein expression in T2DM rats though the protein kinase C (PKC)/extracellular signal-regulated kinase (ERK) signaling pathway.
methodsA T2DM rat model was established using a high-fat and high-sugar diet combined with a low-dose intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into the following five groups: the control group, the untreated T2DM group, the metformin-treated only group, the phorbol 12-myristate 13-acetate (PMA; a PKC agonist administered by intraperitoneal injection) treatment group, and the recombinant human epidermal growth factor (rh-EGF; an ERK agonist administered by tail vein injection) treatment group. The activity of PKC in atrial tissues was assayed by a PKC kinase activity assay kit. The protein expression of SK2, SK3, and phosphorylated ERK (pERK) were determined by western blotting and immunohistochemistry.
resultsCompared with the Control group, atrial PKC activity and pERK and SK3 protein expression were increased, while SK2 protein expression was decreased in atrial tissues of T2DM rats. Eight weeks of metformin treatment inhibited the PKC activity and pERK and SK3 expression, and elevated SK2 expression compared with the T2DM group. Compared with the metformin-treated only group, the injection of rh-EGF increased pERK and SK3 expression, and decreased SK2 expression; the injection of PMA increased PKC activity and SK3 expression, and decreased SK2 expression. In addition, the injection with PMA significantly elevated the expression of pERK.
conclusionsThe PKC/ERK signaling pathway is involved in the downregulation of SK2 expression and the upregulation of SK3 expression in the atrium of T2DM rats. Long-term metformin treatment prevents the SK2 downregulation and the SK3 upregulation through inhibiting the PKC/ERK signaling pathway.
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