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

我们的目标是研究在制造胰岛素的β细胞中保护人们免受糖尿病的自然机制。这将有助于设计可能预防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。它们还产生称为自由基的破坏性副产品，这些副产品被称为超氧化物歧化酶（SOD）的酶灭活。线粒体有自己的DNA，mtDNA，一个制造能量所需的蛋白质蓝图。线粒体DNA的变异通过减少供应给β细胞的能量使糖尿病更容易发生。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，它们就不能容易地再生，这会导致胰岛素缺乏。我们的研究结果可能会提出新的治疗方法，用药物对抗自由基，以防止β细胞的失败。找到一种预防这种损伤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140，000名糖尿病患者和波利尼西亚约95%的人，糖尿病在波利尼西亚非常常见。

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.