Moreira P I, Rolo A P, Sena C, Seiça R, Oliveira C R, Santos M S
Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
Med Chem. 2006 May;2(3):299-308. doi: 10.2174/157340606776930754.
This study evaluated and compared the effect of insulin treatment on the status of brain, heart and kidney mitochondria isolated from 12-week streptozotocin (STZ)-induced diabetic rats versus STZ-diabetic animals treated with insulin during a period of 4 weeks. Mitochondria isolated from 12-week citrate (vehicle)-treated rats were used as control. Several mitochondrial parameters were evaluated: respiratory indexes (state 3 and 4 of respiration, respiratory control and ADP/O ratios), transmembrane potential, depolarization and repolarization levels, ATP, glutathione and coenzyme Q contents, production of hydrogen peroxide, superoxide dismutase, glutathione peroxidase and glutathione reductase activities and the ability of mitochondria to accumulate calcium. We observed that diabetes promoted a significant decrease in kidney and brain mitochondrial coenzyme Q9 content while this parameter was increased in heart mitochondria. Furthermore, diabetes induced a significant increase in hydrogen peroxide production in kidney mitochondria this effect being accompanied by a significant increase in glutathione peroxidase and reductase activities. Furthermore, brain mitochondria isolated from diabetic animals presented a lower ATP content and ability to accumulate calcium. In contrast, heart and kidney mitochondria presented a slight higher capacity to accumulate calcium. Insulin treatment normalized the levels of coenzyme Q9 and glutathione peroxidase and reductase activities and increased ATP content and the ability to accumulate calcium. Altogether these results suggest that insulin treatment attenuates diabetes-induced mitochondrial alterations protecting against the increase in oxidative stress and improving oxidative phosphorylation efficiency. In this line, insulin therapy, besides its well-known importance in the maintenance of glycemic control, may help to protect against mitochondrial dysfunction associated to several age-related disorders such as diabetes.
本研究评估并比较了胰岛素治疗对从12周链脲佐菌素（STZ）诱导的糖尿病大鼠分离的脑、心脏和肾脏线粒体状态的影响，以及与在4周期间接受胰岛素治疗的STZ糖尿病动物的比较。从12周柠檬酸盐（载体）处理的大鼠分离的线粒体用作对照。评估了几个线粒体参数：呼吸指标（呼吸状态3和4、呼吸控制和ADP/O比率）、跨膜电位、去极化和复极化水平、ATP、谷胱甘肽和辅酶Q含量、过氧化氢产生、超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性以及线粒体积累钙的能力。我们观察到糖尿病导致肾脏和脑线粒体辅酶Q9含量显著降低，而该参数在心脏线粒体中增加。此外，糖尿病导致肾脏线粒体过氧化氢产生显著增加，这种效应伴随着谷胱甘肽过氧化物酶和还原酶活性的显著增加。此外，从糖尿病动物分离的脑线粒体呈现较低的ATP含量和积累钙的能力。相比之下，心脏和肾脏线粒体呈现出略高的积累钙的能力。胰岛素治疗使辅酶Q9水平以及谷胱甘肽过氧化物酶和还原酶活性恢复正常，并增加了ATP含量和积累钙的能力。总之，这些结果表明胰岛素治疗减轻了糖尿病诱导的线粒体改变，防止氧化应激增加并提高氧化磷酸化效率。在这方面，胰岛素治疗除了在维持血糖控制方面的众所周知的重要性外，可能有助于预防与几种与年龄相关的疾病如糖尿病相关的线粒体功能障碍。
