ArticlePloS one2015
The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Circulating β-Hydroxybutyrate in Glycemic Progression and Diabetic Cardiomyopathy: Adaptive Signal or Maladaptive Substrate?International journal of molecular sciences · 2026Review
- Effects of exercise training on oxidative phosphorylation-related genes in a diabetic heart via microarray analysis.BMC cardiovascular disorders · 2026Article
- GPR40 activation alleviates pulmonary fibrosis by repressing M2 macrophage polarization through the PKD1/CD36/TGF-β1 pathway.Acta pharmacologica Sinica · 2025Article
- Neurogenic differentiation 2 promotes inflammatory activation of macrophages in doxorubicin-induced myocarditis via regulating protein kinase D.BMC cardiovascular disorders · 2025Article
- Remodelling of cAMP dynamics within the SERCA2a microdomain in heart failure with preserved ejection fraction caused by obesity and type 2 diabetes.Cardiovascular research · 2024Article
- Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity.Nature communications · 2024Article
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Small Molecule Inhibitors of Protein Kinase D: Early Development, Current Approaches, and Future Directions.Journal of medicinal chemistry · 2023Review
- Effects of Short Term Adiponectin Receptor Agonism on Cardiac Function and Energetics in DiabeticJournal of lipid and atherosclerosis · 2022Article
- Cardiac Energy Metabolism in Heart Failure.Circulation research · 2021Review
- Protein Kinase D2 drives chylomicron-mediated lipid transport in the intestine and promotes obesity.EMBO molecular medicine · 2021Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Small-Molecule Inhibitor Targeting Protein Kinase D: A Potential Therapeutic Strategy.Frontiers in oncology · 2021Review
- Loss of protein kinase D activity demonstrates redundancy in cardiac glucose metabolism and preserves cardiac function in obesity.Molecular metabolism · 2020Article
- Increased arrhythmia susceptibility in type 2 diabetic mice related to dysregulation of ventricular sympathetic innervation.American journal of physiology. Heart and circulatory physiology · 2019Article
- Angiogenic function of astragaloside IV in rats with myocardial infarction occurs via the PKD1-HDAC5-VEGF pathway.Experimental and therapeutic medicine · 2019Article
- RNA-Seq Analysis of Islets to Characterise the Dedifferentiation in Type 2 Diabetes Model Mice db/db.Endocrine pathology · 2018Article
- Hyperoxia-induced cardiotoxicity and ventricular remodeling in type-II diabetes mice.Heart and vessels · 2018Article
- Acute and Chronic Effects of Protein Kinase-D Signaling on Cardiac Energy Metabolism.Frontiers in cardiovascular medicine · 2018Review
- Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats.PloS one · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of diabetic cardiomyopathy is a key contributor to heart failure and mortality in obesity and type 2 diabetes (T2D). Current therapeutic interventions for T2D have limited impact on the development of diabetic cardiomyopathy. Clearly, new therapies are urgently needed. A potential therapeutic target is protein kinase D (PKD), which is activated by metabolic insults and implicated in the regulation of cardiac metabolism, contractility and hypertrophy. We therefore hypothesised that PKD inhibition would enhance cardiac function in T2D mice. We first validated the obese and T2D db/db mouse as a model of early stage diabetic cardiomyopathy, which was characterised by both diastolic and systolic dysfunction, without overt alterations in left ventricular morphology. These functional characteristics were also associated with increased PKD2 phosphorylation in the fed state and a gene expression signature characteristic of PKD activation. Acute administration of the PKD inhibitor CID755673 to normal mice reduced both PKD1 and 2 phosphorylation in a time and dose-dependent manner. Chronic CID755673 administration to T2D db/db mice for two weeks reduced expression of the gene expression signature of PKD activation, enhanced indices of both diastolic and systolic left ventricular function and was associated with reduced heart weight. These alterations in cardiac function were independent of changes in glucose homeostasis, insulin action and body composition. These findings suggest that PKD inhibition could be an effective strategy to enhance heart function in obese and diabetic patients and provide an impetus for further mechanistic investigations into the role of PKD in diabetic cardiomyopathy.
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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.