Lynn S, Borthwick G M, Charnley R M, Walker M, Turnbull D M
Department of Medicine, The Medical School, University of Newcastle upon Tyne, Framlington Place, NE2 4HH Newcastle upon Tyne, United Kingdom.
Diabetologia. 2003 Feb;46(2):296-9. doi: 10.1007/s00125-002-1018-z. Epub 2003 Jan 31.
AIMS/HYPOTHESIS: To examine whether there is a high content of mutated mitochondrial DNA in individual pancreatic beta cells from a patient with the A3243G mitochondrial DNA mutation.
Tissues were available from a patient with diabetes and the A3243G mutation including pancreatic tissue. We quantified the amount of mutated mitochondrial DNA in tissue homogenates and single pancreatic beta cells using hot last cycle PCR.
The percentage ratio of mutated to wild-type mtDNA was high in tissues such as muscle and brain (>60%), but surprisingly low in both pancreatic islets and in individual beta cells from these islets. The islets were smaller in the patient than in control subjects in keeping with a decreased beta-cell mass.
CONCLUSIONS/INTERPRETATION: These observations suggest that either the beta cells show increased sensitivity to the effects mtDNA mutations on respiratory chain function, and/or cells with a high mutant load are preferentially removed leading to a progressive decrease in the islet beta-cell mass.
目的/假设：研究患有A3243G线粒体DNA突变的患者个体胰腺β细胞中线粒体DNA突变含量是否较高。
有来自一名患有糖尿病且携带A3243G突变的患者的组织，包括胰腺组织。我们使用热最后循环PCR对组织匀浆和单个胰腺β细胞中的突变线粒体DNA量进行了定量。
在肌肉和大脑等组织中，突变型与野生型线粒体DNA的百分比很高（>60%），但令人惊讶的是，在胰岛以及来自这些胰岛的单个β细胞中该比例很低。与对照组相比，该患者的胰岛较小，这与β细胞量减少一致。
结论/解读：这些观察结果表明，要么β细胞对线粒体DNA突变对呼吸链功能的影响表现出更高的敏感性，和/或具有高突变负荷的细胞被优先清除，导致胰岛β细胞量逐渐减少。
