The importance of mitochondrial oxidative stress on beta cells in type II diabetes

我们的目标是研究在分泌胰岛素的β细胞中保护人们免受糖尿病侵袭的自然机制。这将有助于设计可能防止人们患糖尿病的治疗方法。线粒体是细胞中产生能量的一小部分。它们还会产生被称为自由基的破坏性副产品，这些副产品被一种名为超氧化物歧化酶(SOD)的酶灭活。线粒体有自己的DNA，mtDNA，这是制造能量所需蛋白质的蓝图。线粒体DNA的变异减少了供应给β细胞的能量，从而更有可能导致糖尿病。我们将使用分子技术来降低培养的β细胞中的SOD水平，并确定这是否会增加破坏性自由基的水平。我们将确定这些变化是否会减少胰岛素的产生，因为这可能会导致糖尿病。一旦β细胞受损，它们就不能轻易再生，这就会导致胰岛素缺乏。我们的结果可能会提供新的治疗方法，使用中和自由基的药物来防止β细胞的衰竭。找到一种预防这种损害的治疗方法将改变我们治疗线粒体DNA易患糖尿病的患者的方式。这包括英国的14万糖尿病患者和波利尼西亚约95%的人，那里的糖尿病非常普遍。

We aim to study natural mechanisms that protect people from diabetes in the beta cells that make insulin. This will help design treatments that may prevent people from developing diabetes. Mitochondria are small parts of cells that generate energy. They also generate damaging by-products called free radicals, that are inactivated by an enzyme called superoxide dismutase (SOD). Mitochondria have their own DNA, mtDNA, a blueprint for proteins needed to make energy. Variations in mtDNA make diabetes more likely by reducing the energy supplied to the beta cells. We will use molecular techniques to lower SOD levels in cultured beta cells and determine whether this increases levels of the damaging free radicals. We will determine whether these changes decrease insulin production, as this would make diabetes likely. Once beta cells are damaged they cannot readily be regenerated and this causes insulin deficiency. Our results may suggest novel treatments with drugs that counteract free radicals to prevent failure of the beta cells. Finding a treatment to prevent this damage would change how we treat patients whose mtDNA predisposes them to diabetes. This includes 140,000 diabetics in the UK and ~95% of people in Polynesia, where diabetes is very common.