Hirai M, Suzuki S, Onoda M, Hinokio Y, Hirai A, Ohtomo M, Chiba M, Kasuga S, Hirai S, Satoh Y, Akai H, Miyabayashi S, Toyota T
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
J Clin Endocrinol Metab. 1998 Mar;83(3):992-4. doi: 10.1210/jcem.83.3.4643.
Accumulating reports indicate a relationship between mitochondrial DNA mutation and impaired glucose-induced insulin secretion leading to a subtype of noninsulin-dependent diabetes mellitus. DNA from a 45-yr-old Japanese woman with noninsulin-dependent diabetes mellitus and muscle atrophy was isolated and studied for mitochondrial DNA mutations. We identified a mitochondrial DNA C-T heteroplasmic mutation at nucleotide position 3256. The mutation was located in the transfer ribonucleic acidLeu in a region conserved in evolution. Eight other members of her family were examined for the mutation. Six of them had the same mutation together with noninsulin-dependent diabetes mellitus, and one teenage boy had the mutation and impaired glucose tolerance. The other family member who did not have this mutation had normal glucose tolerance. The enzyme activity of the mitochondrial oxidative phosphorylation pathway in the muscle of the proband was measured. The enzyme activity was decreased in the proband, especially in complex I. This mutation might be responsible for the abnormal glucose metabolism.
越来越多的报告表明，线粒体DNA突变与葡萄糖诱导的胰岛素分泌受损之间存在关联，进而导致非胰岛素依赖型糖尿病的一种亚型。从一名患有非胰岛素依赖型糖尿病和肌肉萎缩的45岁日本女性身上分离出DNA，并对其线粒体DNA突变进行研究。我们在核苷酸位置3256处鉴定出线粒体DNA的C-T异质性突变。该突变位于进化保守区域的亮氨酸转运核糖核酸中。对她家族中的其他八名成员进行了该突变检测。其中六人患有相同突变及非胰岛素依赖型糖尿病，一名十几岁男孩有该突变且葡萄糖耐量受损。另一名未携带此突变的家族成员葡萄糖耐量正常。对先证者肌肉中线粒体氧化磷酸化途径的酶活性进行了测量。先证者的酶活性降低，尤其是在复合体I中。这种突变可能是异常葡萄糖代谢的原因。
