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Glucose fluctuation accelerates cardiac injury of diabetic mice via sodium-dependent glucose cotransporter 1 (SGLT1)
Archives of Biochemistry and Biophysics ( IF 3.9 ) Pub Date : 2021-06-18 , DOI: 10.1016/j.abb.2021.108968
Weihua Wu 1 , Qian Chai 2 , Ziying Zhang 2
Affiliation  

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.



中文翻译:

葡萄糖波动通过钠依赖性葡萄糖协同转运蛋白 1 (SGLT1) 加速糖尿病小鼠的心脏损伤

最近的研究表明,血糖波动与糖尿病(DM)并发症有关。SGLT1(钠依赖性葡萄糖协同转运蛋白1)在心脏病理状态下高表达,在高糖诱导的心肌细胞中表达。在此,我们构建了一个具有葡萄糖波动的糖尿病小鼠模型,以研究 SGLT1 是否参与了葡萄糖波动引起的心脏损伤。进行超声心动图、组织学检查和 TUNEL 染色以评估心脏功能障碍和损伤。为了评估葡萄糖波动引起的氧化应激,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。评估线粒体功能障碍、线粒体膜电位 (MMP)、ATP 含量、线粒体呼吸链复合体活性,以及​​线粒体融合和裂变蛋白的表达被确定。结果表明,血糖波动的糖尿病小鼠出现心脏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 的敲低可以消除葡萄糖波动对心脏损伤的影响。因此,我们的研究强调 SGLT1 在葡萄糖波动引起的氧化应激和线粒体功能障碍引起的心脏损伤中发挥重要作用。氧化应激和线粒体功能障碍。SGLT1 的敲低可以消除葡萄糖波动对心脏损伤的影响。因此,我们的研究强调 SGLT1 在葡萄糖波动引起的氧化应激和线粒体功能障碍引起的心脏损伤中发挥重要作用。氧化应激和线粒体功能障碍。SGLT1 的敲低可以消除葡萄糖波动对心脏损伤的影响。因此,我们的研究强调 SGLT1 在葡萄糖波动引起的氧化应激和线粒体功能障碍引起的心脏损伤中发挥重要作用。

更新日期:2021-06-25
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