ArticleJournal of cardiovascular pharmacology2011
Restoration of defective L-type Ca2+ current in cardiac myocytes of type 2 diabetic db/db mice by Akt and PKC-ι.
Article in Journal of cardiovascular pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- Experimental Models for Studying Cardiovascular Dysfunction in Metabolic Syndrome.Handbook of experimental pharmacology · 2026Review
- Experimental Models for Studying Cardiovascular Dysfunction in Metabolic Syndrome.Handbook of experimental pharmacology · 2026Review
- The association of QTc prolongation with cardiovascular events in cancer patients taking tyrosine kinase inhibitors (TKIs).Cardio-oncology (London, England) · 2023Article
- Advanced glycation end products modulate electrophysiological remodeling of right ventricular outflow tract cardiomyocytes: A novel target for diabetes-related ventricular arrhythmogenesis.Physiological reports · 2022Article
- Diabetic Cardiomyopathy: Pathophysiology and Novel Therapies.The Brown journal of hospital medicine · 2022Review
- Diabetes-induced changes in cardiac voltage-gated ion channels.World journal of diabetes · 2021Review
- Intracellular O-linked glycosylation directly regulates cardiomyocyte L-type CaBasic research in cardiology · 2020Article
- PKC and PKN in heart disease.Journal of molecular and cellular cardiology · 2019Review
- Effect of omentin on cardiovascular functions and gene expressions in isolated rat hearts.Anatolian journal of cardiology · 2019Article
- The Effect of Chemerin on Cardiac Parameters and Gene Expressions in Isolated Perfused Rat HeartBalkan medical journal · 2019Article
- Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity.Frontiers in physiology · 2018Review
- Troxerutin protects against diabetic cardiomyopathy through NF‑κB/AKT/IRS1 in a rat model of type 2 diabetes.Molecular medicine reports · 2017Article
- Prevalence of QT prolongation and associated LVEF changes in diabetic patients over a four-year retrospective time period.Journal of community hospital internal medicine perspectives · 2017Article
- Control of cardiac repolarization by phosphoinositide 3-kinase signaling to ion channels.Circulation research · 2015Review
- Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation.The Journal of clinical investigation · 2014Article
- Increased persistent sodium current due to decreased PI3K signaling contributes to QT prolongation in the diabetic heart.Diabetes · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetes is associated with an increased risk of heart failure and the development of a cardiomyopathy whose etiology is only partially understood. Ca entry through the voltage-dependent L-type Ca channel CaV1.2 initiates the contractile cycle in cardiac myocytes. Decreased cardiac contractility and depressed CaV1.2 function have been reported in obese type 2 diabetic db/db mice. Here, we demonstrate that a reduction in phosphoinositide 3-kinase (PI3K) signaling is a major contributor to the altered function of CaV1.2 in db/db cardiac myocytes. Using the whole-cell patch clamp technique, we determined that intracellular infusion of cardiac myocytes from db/db mice with phosphatidylinositol 3,4,5-trisphosphate (PIP3), the second messenger produced by PI3K, increased the L-type Ca current (ICa,L) density nearly to the level seen in wild-type cells. PIP3 also reversed the positive shift in the voltage dependence of the steady-state current activation observed in db/db myocytes. Infusion of protein kinases that act downstream of PI3K also affected ICa,L. Akt1 and Akt2 were as effective as PIP3 in restoring the ICa,L density in db/db myocytes but did not affect the voltage dependence of current activation. The infusion of atypical PKC-ι (the human homolog of mouse PKC-λ) caused a small but significant increase in the ICa,L density and completely reversed the shift in voltage dependence of steady-state current activation. These results indicate that a defect in PI3K/PIP3/Akt/PKC-λ signaling is mainly responsible for the depressed CaV1.2 function in the hearts of db/db mice with type 2 diabetes.
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