Glucose transporters in cardiovascular system in health and disease
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INVITED REVIEW
Glucose transporters in cardiovascular system in health and disease Luc Bertrand 1 & Julien Auquier 1 & Edith Renguet 1 & Marine Angé 1 & Julien Cumps 1 & Sandrine Horman 1 & Christophe Beauloye 1,2 Received: 24 June 2020 / Revised: 28 July 2020 / Accepted: 31 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Glucose transporters are essential for the heart to sustain its function. Due to its nature as a high energy-consuming organ, the heart needs to catabolize a huge quantity of metabolic substrates. For optimized energy production, the healthy heart constantly switches between various metabolites in accordance with substrate availability and hormonal status. This metabolic flexibility is essential for the maintenance of cardiac function. Glucose is part of the main substrates catabolized by the heart and its use is fine-tuned via complex molecular mechanisms that include the regulation of the glucose transporters GLUTs, mainly GLUT4 and GLUT1. Besides GLUTs, glucose can also be transported by cotransporters of the sodium-glucose cotransporter (SGLT) (SLC5 gene) family, in which SGLT1 and SMIT1 were shown to be expressed in the heart. This SGLT-mediated uptake does not seem to be directly linked to energy production but is rather associated with intracellular signalling triggering important processes such as the production of reactive oxygen species. Glucose transport is markedly affected in cardiac diseases such as cardiac hypertrophy, diabetic cardiomyopathy and heart failure. These alterations are not only fingerprints of these diseases but are involved in their onset and progression. The present review will depict the importance of glucose transport in healthy and diseased heart, as well as proposed therapies targeting glucose transporters. Keywords Cardiac metabolism . GLUT . SGLT . SMIT1 . Akt . AMPK . Glucotoxicity . Diabetic cardiomyopathy . Cardiac hypertrophy . Heart failure
Introduction The heart is an astonishing organ that requires lots of energy to sustain its pumping function. Every single d a y, t h e le f t ve n t r i c l e o f a h u m a n h e a r t ej ec t s approximatively 8 tons of blood for 100,000 beatings. Such heavy work needs a tremendous mass of energy. Not less than 6 kg of ATP, the main cellular energyproviding molecule, is utilized by the heart in 24 h, This article is part of the special issue on Glucose Transporters in Health and Disease in Pflügers Archiv—European Journal of Physiology * Luc Bertrand [email protected] 1
Institut de Recherche Expérimentale et Clinique, Pole of Cardiovascular Research, Université catholique de Louvain, Avenue Hippocrate 55, B1.55.05, B-1200 Brussels, Belgium
2
Division of Cardiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
corresponding to 20 times its own weight. This makes the heart the most energy-consuming organ (per unit weight) of the human body [70]. Due to the lack of a significant store of energy (the heart possesses a level of ATP for few seconds and metabolic store, s
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