Qi Dake, Rodrigues Brian
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E654-67. doi: 10.1152/ajpendo.00453.2006. Epub 2006 Oct 31.
Insulin resistance is viewed as an insufficiency in insulin action, with glucocorticoids being recognized to play a key role in its pathogenesis. With insulin resistance, metabolism in multiple organ systems such as skeletal muscle, liver, and adipose tissue is altered. These metabolic alterations are widely believed to be important factors in the morbidity and mortality of cardiovascular disease. More importantly, clinical and experimental studies have established that metabolic abnormalities in the heart per se also play a crucial role in the development of heart failure. Following glucocorticoids, glucose utilization is compromised in the heart. This attenuated glucose metabolism is associated with altered fatty acid supply, composition, and utilization. In the heart, elevated fatty acid use has been implicated in a number of metabolic, morphological, and mechanical changes and, more recently, in "lipotoxicity". In the present article, we review the action of glucocorticoids, their role in insulin resistance, and their influence in modulating peripheral and cardiac metabolism and heart disease.
胰岛素抵抗被视为胰岛素作用不足,糖皮质激素在其发病机制中被认为起关键作用。存在胰岛素抵抗时,骨骼肌、肝脏和脂肪组织等多个器官系统的代谢会发生改变。这些代谢改变被广泛认为是心血管疾病发病和死亡的重要因素。更重要的是,临床和实验研究已证实,心脏本身的代谢异常在心力衰竭的发展中也起关键作用。使用糖皮质激素后,心脏的葡萄糖利用受到损害。这种减弱的葡萄糖代谢与脂肪酸供应、组成和利用的改变有关。在心脏中,脂肪酸利用增加与多种代谢、形态和机械变化有关,最近还与“脂毒性”有关。在本文中,我们综述了糖皮质激素的作用、它们在胰岛素抵抗中的作用以及它们对外周和心脏代谢及心脏病的调节影响。