Kansakar Urna, Nieves Garcia Crystal, Santulli Gaetano, Gambardella Jessica, Mone Pasquale, Jankauskas Stanislovas S, Lombardi Angela
Department of Molecular Pharmacology, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Einstein Institute for Neuroimmunology and Inflammation (INI), Albert Einstein College of Medicine, New York, NY 10461, USA.
Department of Medicine, Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, NY 10461, USA.
J Clin Med. 2024 Dec 4;13(23):7391. doi: 10.3390/jcm13237391.
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.
酮体是肝脏中由脂肪酸产生的分子，当血糖水平较低时，它们作为能量载体输送到外周组织。已知碳水化合物和热量限制饮食会增加循环酮体水平，近年来，由于其对多种疾病可能具有的健康益处而备受关注。具体而言，据报道通过饮食调节增加酮体对心血管健康有益，并能改善葡萄糖稳态和胰岛素抵抗。有趣的是，虽然酮体产生过多可能会在糖尿病患者中导致危及生命的酮症酸中毒，但越来越多的证据表明，适度水平的酮体在胰腺β细胞中发挥适应性和有益作用，尽管确切机制仍不清楚。值得注意的是，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂已被证明可提高β-羟基丁酸（BHB）的水平，BHB是人体中循环最丰富的酮体，它可能在介导其对心血管健康和糖尿病的一些保护作用中发挥关键作用。本系统综述全面概述了科学文献，并分析了酮体对心血管病理生理学和胰腺β细胞功能的影响。临床前和临床研究的证据表明，外源性酮体可能对心肌细胞和胰腺β细胞都有显著的有益作用，使其成为潜在心脏保护疗法以及保护糖尿病患者β细胞功能的有趣候选物。
