Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Diabetes Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Toxicol Lett. 2019 Feb;301:24-33. doi: 10.1016/j.toxlet.2018.10.025. Epub 2018 Oct 29.
A large body of evidence indicates that accumulation of oxidative stress originated from impaired mitochondrial respiratory chain is the main cause for the development of numerous diseases including diabetes and cancer. Arsenic exposure is a potential risk factor for type 2 diabetes development which, by disrupting mitochondrial respiration and SirT3 enzyme activity, enhances reactive oxygen species (ROS) level and evokes oxidative stress. In this study the impact of arsenic exposure on the mitochondrial function and SirT3 from rat's liver were examined in the presence or absence of metformin and berberine.
Serum glucose and insulin levels were assessed in rats exposed to the diabetogenic concentration of arsenic. Isolated hepatocytes and mitochondria were then further evaluated to determine any deleterious consequences.
Diabetogenesis triggered by arsenic contributed to the mitochondrial ROS overproduction, impaired complex II activity, glucose homeostasis, glucose tolerance and insulin sensitivity. An increased SirT3 level indicated the compensatory mechanism to deal with this condition. Protective effect of metformin and berberine against these toxic insults were found to be associated with the mitochondrial SirT3 pathway. This pathway through the regulation of mitochondria-associated ROS production and glucose homeostasis in the liver may play a crucial role against the diabetogenic effect of arsenic.
大量证据表明，源自受损线粒体呼吸链的氧化应激积累是包括糖尿病和癌症在内的许多疾病发展的主要原因。砷暴露是 2 型糖尿病发展的潜在危险因素，它通过破坏线粒体呼吸和 SirT3 酶活性，增加活性氧（ROS）水平并引发氧化应激。在这项研究中，研究了在存在或不存在二甲双胍和小檗碱的情况下，砷暴露对大鼠肝脏线粒体功能和 SirT3 的影响。
检测接触致糖尿病浓度砷的大鼠的血清葡萄糖和胰岛素水平。然后进一步评估分离的肝细胞和线粒体，以确定任何有害后果。
砷引发的糖尿病发生导致线粒体 ROS 过度产生、复合物 II 活性受损、葡萄糖稳态、葡萄糖耐量和胰岛素敏感性降低。SirT3 水平升高表明存在代偿机制来应对这种情况。发现二甲双胍和小檗碱对这些毒性损伤的保护作用与线粒体 SirT3 途径有关。该途径通过调节肝脏中线粒体相关 ROS 的产生和葡萄糖稳态，可能在对抗砷的致糖尿病作用方面发挥关键作用。
