ArticleCardiovascular diabetology2018
Inhibition of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic rats.
Article in Cardiovascular diabetology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 53 citations in OpenAlex.
- Maternal hyperglycemia-induced O-GlcNAcylation of CaMKIIδ promotes mtDNA release and cardiac remodeling in offspring.Nature communications · 2026Article
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- Mechanotransduction Failure and Molecular Rescue in Gastric Cancer: Kinetotherapy Across the IL-6/STAT3-Myostatin/ACVR2B-Akt/mTOR Axis.Medical sciences (Basel, Switzerland) · 2026Review
- The Calmodulin/Striatin Interaction Is Enhanced in Diabetic Hearts and Defines Novel Signaling Clusters Implicated in Cardiac Remodeling.ACS omega · 2026Article
- CaPhysiological reports · 2026Article
- Salivary proteomics of patients with type 2 diabetes identify potential biomarkers for diabetes and highlight significant role of immune response.Clinical and experimental medicine · 2026Article
- Impact of left ventricular dilatation on biventricular function and deformation in diabetes mellitus with reduced ejection fraction: a CMR feature tracking study.Cardiovascular diabetology · 2025Article
- Right ventricular dysfunctions in type 1 diabetic mice: A longitudinal study.World journal of diabetes · 2025Article
- Calcium Signaling and Cardiac Adaptation to Stress: Focus on Pregnancy and Diabetes.Biomolecules · 2025Review
- Computational modelling for improved translation of cardiac inotropic and lusitropic drug effects from rats to humans.Journal of pharmacological and toxicological methods · 2025Article
- S-nitrosylation of cardiac myocyte proteins may underlie sex differences in cardiac disease.Frontiers in physiology · 2025Review
- Comparison between the protective effect of the orally administered atorvastatin and safflower (Frontiers in pharmacology · 2025Article
- Post-translational modifications in diabetic cardiomyopathy.Journal of cellular and molecular medicine · 2024Review
- Role of CaMKII in diabetes induced vascular injury and its interaction with anti-diabetes therapy.Reviews in endocrine & metabolic disorders · 2024Review
- Regulation of Smooth Muscle Cell Proliferation by Mitochondrial Ca2+ in Type 2 Diabetes.International journal of molecular sciences · 2023Article
- Article
- Differential changes in cyclic adenosine 3'-5' monophosphate (cAMP) effectors and major CaJournal of cellular and molecular medicine · 2023Article
- The right ventricular dysfunction and ventricular interdependence in patients with DM: assessment using cardiac MR feature tracking.Cardiovascular diabetology · 2023Article
- Article
- The mitochondrial regulation of smooth muscle cell proliferation in type 2 diabetes.bioRxiv : the preprint server for biology · 2023Article
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9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCalcium/calmodulin-dependent kinase II-delta (CaMKIIδ) activity is enhanced during hyperglycemia and has been shown to alter intracellular calcium handling in cardiomyocytes, ultimately leading to reduced cardiac performance. However, the effects of CaMKIIδ on cardiac contractility during type 2 diabetes are undefined.
methodsWe examined the expression and activation of CaMKIIδ in right atrial appendages from non-diabetic and type 2 diabetic patients (n = 7 patients per group) with preserved ejection fraction, and also in right ventricular tissue from Zucker Diabetic Fatty rats (ZDF) (n = 5-10 animals per group) during early diabetic cardiac dysfunction, using immunoblot. We also measured whole heart function of ZDF and control rats using echocardiography. Then we measured contraction and relaxation parameters of isolated trabeculae from ZDF to control rats in the presence and absence of CaMKII inhibitors.
resultsCaMKIIδ phosphorylation (at Thr287) was increased in both the diabetic human and animal tissue, indicating increased CaMKIIδ activation in the type 2 diabetic heart. Basal cardiac contractility and relaxation were impaired in the cardiac muscles from the diabetic rats, and CaMKII inhibition with KN93 partially restored contractility and relaxation. Autocamtide-2-related-inhibitor peptide (AIP), another CaMKII inhibitor that acts via a different mechanism than KN93, fully restored cardiac contractility and relaxation.
conclusionsOur results indicate that CaMKIIδ plays a key role in modulating performance of the diabetic heart, and moreover, suggest a potential therapeutic role for CaMKII inhibitors in improving myocardial function during type 2 diabetes.
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