Department of General Medicine, The Third Affiliated Hospital of Shenzhen University, Shenzhen 518001, People's Republic of China.
Department of General Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, People's Republic of China.
Arch Biochem Biophys. 2021 Sep 30;709:108968. doi: 10.1016/j.abb.2021.108968. Epub 2021 Jun 18.
Recent studies have shown that blood glucose fluctuation is associated with complications of diabetes mellitus (DM). SGLT1 (sodium-dependent glucose cotransporter 1), is highly expressed in pathological conditions of heart, and is expressed in cardiomyocytes induced by high glucose. Herein, we constructed a diabetic mouse model with glucose fluctuation to investigate whether SGLT1 is involved in glucose fluctuation-induced cardiac injury. Echocardiography, histology examination, and TUNEL staining were performed to evaluate cardiac dysfunction and damage. To assess glucose fluctuation-induced oxidative stress, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. To assess mitochondrial dysfunction, mitochondrial membrane potential (MMP), ATP content, mitochondrial respiratory chain complex activity, and expression of mitochondrial fusion and fission proteins were determined. The results indicated that diabetic mice with glucose fluctuation showed elevation of cardiac SGLT1 expression, left ventricular dysfunction, oxidative stress and mitochondrial dysfunction. Knockdown of SGLT1 could abrogate the effects of glucose fluctuation on cardiac injury. Thus, our study highlighted that SGLT1 plays an important role in glucose fluctuation induced cardiac injury through oxidative stress and mitochondrial dysfunction.
最近的研究表明，血糖波动与糖尿病（DM）的并发症有关。SGLT1（钠依赖性葡萄糖共转运蛋白 1）在心脏的病理条件下高度表达，并在高葡萄糖诱导的心肌细胞中表达。在此，我们构建了一种具有血糖波动的糖尿病小鼠模型，以研究 SGLT1 是否参与血糖波动诱导的心脏损伤。通过超声心动图、组织学检查和 TUNEL 染色来评估心脏功能障碍和损伤。为了评估血糖波动诱导的氧化应激，测量了活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH）的水平。为了评估线粒体功能障碍，测定了线粒体膜电位（MMP）、ATP 含量、线粒体呼吸链复合体活性以及线粒体融合和分裂蛋白的表达。结果表明，具有血糖波动的糖尿病小鼠表现出心脏 SGLT1 表达升高、左心室功能障碍、氧化应激和线粒体功能障碍。SGLT1 的敲低可以消除血糖波动对心脏损伤的影响。因此，我们的研究强调了 SGLT1 通过氧化应激和线粒体功能障碍在血糖波动诱导的心脏损伤中发挥重要作用。
