Treatments for skeletal muscle abnormalities in heart failure: sodium-glucose transporter 2 and ketone bodies
Treatments for skeletal muscle abnormalities in heart failure: sodium-glucose transporter 2 and ketone bodies
复制标题
心力衰竭骨骼肌异常的治疗：钠-葡萄糖转运蛋白 2 和酮体
DOI：
10.1152/ajpheart.00100.2021
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
Kinugawa Shintaro
中科院分区：
文献类型：
--
作者：
Takada Shingo;Sabe Hisataka;Kinugawa Shintaro
已知各种骨骼肌异常发生在心力衰竭（HF）中，并与运动不耐受密切相关。特别是，由骨骼肌中的线粒体功能障碍引起的异常能量代谢是耐力运动能力降低的原因。然而，到目前为止，没有特定的药物治疗已经建立了骨骼肌异常和运动不耐受发生在HF患者。钠-葡萄糖转运蛋白2（SGLT 2）抑制剂通过抑制肾小管中的葡萄糖重吸收促进葡萄糖排泄，其具有不依赖于胰岛素分泌的降血糖作用。最近，大型临床试验表明，SGLT 2抑制剂治疗可抑制心力衰竭伴收缩功能障碍患者的心血管事件。SGLT 2抑制剂对HF的治疗作用机制被认为是利尿、抑制神经体液因子激活、肾保护和改善心肌代谢，但迄今为止尚未阐明。已知SGLT 2抑制剂可增加血酮体。这表明它们可能改善HF中异常的骨骼肌代谢，即改善脂肪酸代谢，抑制糖酵解，并在线粒体能量产生中使用酮体。最终，它们可以改善骨骼肌的有氧代谢，抑制无氧代谢，并在无氧阈值水平上提高有氧运动能力。这些SGLT 2抑制剂的潜在作用解释了它们在HF中的有效性，并可能成为旨在改善运动不耐受的新药治疗的候选药物。在这篇综述中，我们概述了SGLT 2抑制剂对骨骼肌代谢的影响，特别关注酮代谢。
Various skeletal muscle abnormalities are known to occur in heart failure (HF) and are closely associated with exercise intolerance. Particularly, abnormal energy metabolism caused by mitochondrial dysfunction in skeletal muscle is a cause of decreased endurance exercise capacity. However, to date, no specific drug treatment has been established for the skeletal muscle abnormalities and exercise intolerance occurring in patients with HF. Sodium-glucose transporter 2 (SGLT2) inhibitors promote glucose excretion by suppressing glucose reabsorption in the renal tubules, which has a hypoglycemic effect independent of insulin secretion. Recently, large clinical trials have demonstrated that treatment with SGLT2 inhibitors suppresses cardiovascular events in patients who have HF with systolic dysfunction. Mechanisms of the therapeutic effects of SGLT2 inhibitors for HF have been suggested to be diuretic, suppression of neurohumoral factor activation, renal protection, and improvement of myocardial metabolism, but this has not been clarified to date. SGLT2 inhibitors are known to increase blood ketone bodies. This suggests that they may improve the abnormal skeletal muscle metabolism in HF, that is, improve fatty acid metabolism, suppress glycolysis, and use ketone bodies in mitochondrial energy production. Ultimately, they may improve aerobic metabolism in skeletal muscle, suppress anaerobic metabolism, and improve aerobic exercise capacity at the level of the anaerobic threshold. The potential actions of such SGLT2 inhibitors explain their effectiveness in HF and may be candidates for new drug treatments aimed at improving exercise intolerance. In this review, we outlined the effects of SGLT2 inhibitors on skeletal muscle metabolism, with a particular focus on ketone metabolism.