INHIBITORY EFFECT OF ^|^beta;-HYDROXYBUTYRIC ACID ON L-TYPE Ca2+ CURRENT UNDER ^|^beta;-ADRENERGIC STIMULATION IN GUINEA PIG CARDIAC VENTRICULAR MYOCYTES

Kurihara, Masato; Akama, Youichi; Kimura, Junko

doi:10.5387/fms.58.144

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…Some epilepsy patients may have abnormal transcellular membrane ion channels resulting in a predisposition to develop conduction abnormalities as seen in those who develop long QT on cisapride, tricyclics, or class I and III antiarrhythmics (Best et al, 2000). One study revealed that β-OHB at high concentrations (10 mM) reduced L-type Ca 2+ current in guinea pig ventricular myocytes but only in the presence of the β–adrenergic agonist isoproterenol, however it had no effect on L-type Ca 2+ current under basal conditions (Kurihara et al, 2012). Another study suggested that the L-stereoisomer of β-OHB could block the transient outward K + current ( I to ) in murine ventricular myocytes causing action potential prolongation (Doepner et al, 1997) while D-β-OHB had no effect.…”

Section: Role Of β-Ohb In Cardiovascular Health and Diseasementioning

confidence: 99%

Role of Î²-hydroxybutyrate, its polymer poly-Î²-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease

2014

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We provide a comprehensive review of the role of β-hydroxybutyrate (β-OHB), its linear polymer poly-β-hydroxybutyrate (PHB), and inorganic polyphosphate (polyP) in mammalian health and disease. β-OHB is a metabolic intermediate that constitutes 70% of ketone bodies produced during ketosis. Although ketosis has been generally considered as an unfavorable pathological state (e.g., diabetic ketoacidosis in type-1 diabetes mellitus), it has been suggested that induction of mild hyperketonemia may have certain therapeutic benefits. β-OHB is synthesized in the liver from acetyl-CoA by β-OHB dehydrogenase and can be used as alternative energy source. Elevated levels of PHB are associated with pathological states. In humans, short-chain, complexed PHB (cPHB) is found in a wide variety of tissues and in atherosclerotic plaques. Plasma cPHB concentrations correlate strongly with atherogenic lipid profiles, and PHB tissue levels are elevated in type-1 diabetic animals. However, little is known about mechanisms of PHB action especially in the heart. In contrast to β-OHB, PHB is a water-insoluble, amphiphilic polymer that has high intrinsic viscosity and salt-solvating properties. cPHB can form non-specific ion channels in planar lipid bilayers and liposomes. PHB can form complexes with polyP and Ca2+ which increases membrane permeability. The biological roles played by polyP, a ubiquitous phosphate polymer with ATP-like bonds, have been most extensively studied in prokaryotes, however polyP has recently been linked to a variety of functions in mammalian cells, including blood coagulation, regulation of enzyme activity in cancer cells, cell proliferation, apoptosis and mitochondrial ion transport and energy metabolism. Recent evidence suggests that polyP is a potent activator of the mitochondrial permeability transition pore in cardiomyocytes and may represent a hitherto unrecognized key structural and functional component of the mitochondrial membrane system.

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Section: Role Of β-Ohb In Cardiovascular Health and Diseasementioning

confidence: 99%

Role of Î²-hydroxybutyrate, its polymer poly-Î²-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease

2014

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The effects of the ketone body β-hydroxybutyrate on isolated rat ventricular myocyte excitation-contraction coupling

Klos

Morgenstern

Hicks

et al. 2019

Archives of Biochemistry and Biophysics

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Exogenous Ketones in Cardiovascular Disease and Diabetes: From Bench to Bedside

Kansakar,

Nieves Garcia,

Santulli

et al. 2024

JCM

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Ketone bodies are molecules produced from fatty acids in the liver that act as energy carriers to peripheral tissues when glucose levels are low. Carbohydrate- and calorie-restricted diets, known to increase the levels of circulating ketone bodies, have attracted significant attention in recent years due to their potential health benefits in several diseases. Specifically, increasing ketones through dietary modulation has been reported to be beneficial for cardiovascular health and to improve glucose homeostasis and insulin resistance. Interestingly, although excessive production of ketones may lead to life-threatening ketoacidosis in diabetic patients, mounting evidence suggests that modest levels of ketones play adaptive and beneficial roles in pancreatic beta cells, although the exact mechanisms are still unknown. Of note, Sodium-Glucose Transporter 2 (SGLT2) inhibitors have been shown to increase the levels of beta-hydroxybutyrate (BHB), the most abundant ketone circulating in the human body, which may play a pivotal role in mediating some of their protective effects in cardiovascular health and diabetes. This systematic review provides a comprehensive overview of the scientific literature and presents an analysis of the effects of ketone bodies on cardiovascular pathophysiology and pancreatic beta cell function. The evidence from both preclinical and clinical studies indicates that exogenous ketones may have significant beneficial effects on both cardiomyocytes and pancreatic beta cells, making them intriguing candidates for potential cardioprotective therapies and to preserve beta cell function in patients with diabetes.

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INHIBITORY EFFECT OF ^|^beta;-HYDROXYBUTYRIC ACID ON L-TYPE Ca2+ CURRENT UNDER ^|^beta;-ADRENERGIC STIMULATION IN GUINEA PIG CARDIAC VENTRICULAR MYOCYTES

Cited by 3 publications

References 31 publications

Role of Î²-hydroxybutyrate, its polymer poly-Î²-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease

Role of Î²-hydroxybutyrate, its polymer poly-Î²-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease

The effects of the ketone body β-hydroxybutyrate on isolated rat ventricular myocyte excitation-contraction coupling

Exogenous Ketones in Cardiovascular Disease and Diabetes: From Bench to Bedside

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