Morten Karl J, Potter Michelle, Badder Luned, Sivathondan Pamela, Dragovic Rebecca, Neumann Abigale, Gavin James, Shrestha Roshan, Reilly Svetlana, Phadwal Kanchan, Lodge Tiffany A, Borzychowski Angela, Cookson Sharon, Mitchell Corey, Morovat Alireza, Simon Anna Katharina, Uusimaa Johanna, Hynes James, Poulton Joanna
Nuffield Department of Obstetrics & Gynaecology, The Women's Centre, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, UK.
Wellcome Open Res. 2019 Sep 25;2:14. doi: 10.12688/wellcomeopenres.10535.3. eCollection 2017.
Mitochondrial diabetes is primarily caused by β-cell failure, a cell type whose unique properties are important in pathogenesis. By reducing glucose, we induced energetic stress in two rodent β-cell models to assess effects on cellular function. Culturing rat insulin-secreting INS-1 cells in low glucose conditions caused a rapid reduction in whole cell respiration, associated with elevated mitochondrial reactive oxygen species production, and an altered glucose-stimulated insulin secretion profile. Prolonged exposure to reduced glucose directly impaired mitochondrial function and reduced autophagy. Insulinoma cell lines have a very different bioenergetic profile to many other cell lines and provide a useful model of mechanisms affecting β-cell mitochondrial function.
线粒体糖尿病主要由β细胞功能衰竭引起，β细胞是一种其独特特性在发病机制中很重要的细胞类型。通过降低葡萄糖水平，我们在两种啮齿动物β细胞模型中诱导能量应激，以评估对细胞功能的影响。在低葡萄糖条件下培养大鼠胰岛素分泌型INS-1细胞导致全细胞呼吸迅速降低，这与线粒体活性氧生成增加以及葡萄糖刺激的胰岛素分泌模式改变有关。长时间暴露于降低的葡萄糖水平直接损害线粒体功能并减少自噬。胰岛素瘤细胞系与许多其他细胞系具有非常不同的生物能量特征，为影响β细胞线粒体功能的机制提供了一个有用的模型。
