Hirose Masamichi, Matsushita Naoko, Ishida Nanae, Ibi Miho, Saito Maki
School of Pharmaceutical Sciences, Iwate Medical University.
School of Medicine, Iwate Medical University.
Yakugaku Zasshi. 2018;138(7):939-943. doi: 10.1248/yakushi.17-00223-2.
It is well-known that metabolic remodeling occurs in the presence of cardiomyopathy induced by cardiac ischemia and hypertrophy, and diabetes mellitus. It is also known that a novel cardiac glucose transporter, sodium-glucose co-transporter 1 (SGLT1), is expressed in the human heart. However, the role of SGLT1 in the development of cardiac metabolic remodeling is still unclear. Recent studies demonstrated that SGLT1 activation improves ischemia-reperfusion-induced cardiac injury, and increased SGLT1 gene expression is observed in hypertrophic, ischemic, and diabetic cardiomyopathy in human hearts. Moreover, increases in SGLT1 protein expression cause cardiac remodeling such as hypertrophy and increased interstitial fibrosis in mice. We demonstrated that ischemia-reperfusion-induced cardiac injury was potentiated in SGLT1-deficient mice. In contrast, chronic pressure overload induced by transverse aortic constriction (TAC) caused cardiac hypertrophy and reduced left ventricular fractional shortening in C57BL/6J wild-type mice. Moreover, the TAC-induced hypertrophied heart showed increased SGLT1 and AMPKαprotein expressions. These results suggest the different effects of SGLT1 activation on cardiac diseases such as acute ischemia-reperfusion-induced cardiac injury and chronically-induced cardiac hypertrophy. Thus, SGLT1 may be a novel therapeutic target for the treatment of patients with cardiac diseases such as ischemic and hypertrophic cardiomyopathy.
众所周知，在由心脏缺血、肥大以及糖尿病引起的心肌病中会发生代谢重塑。还已知一种新型心脏葡萄糖转运体——钠-葡萄糖协同转运蛋白1（SGLT1）在人类心脏中表达。然而，SGLT1在心脏代谢重塑发展中的作用仍不清楚。最近的研究表明，SGLT1激活可改善缺血-再灌注诱导的心脏损伤，并且在人类心脏的肥厚性、缺血性和糖尿病性心肌病中观察到SGLT1基因表达增加。此外，SGLT1蛋白表达增加会导致小鼠心脏重塑，如肥大和间质纤维化增加。我们证明，在SGLT1缺陷小鼠中，缺血-再灌注诱导的心脏损伤会增强。相比之下，横断主动脉缩窄（TAC）引起的慢性压力过载会导致C57BL/6J野生型小鼠心脏肥大并降低左心室缩短分数。此外，TAC诱导的肥大心脏显示SGLT1和AMPKα蛋白表达增加。这些结果表明SGLT1激活对诸如急性缺血-再灌注诱导的心脏损伤和慢性诱导的心脏肥大等心脏疾病具有不同影响。因此，SGLT1可能是治疗诸如缺血性和肥厚性心肌病等心脏病患者的新型治疗靶点。
