Maassen J A, van Essen E, van den Ouweland J M, Lemkes H H
Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Exp Clin Endocrinol Diabetes. 2001;109(3):127-34. doi: 10.1055/s-2001-14834.
This review provides a compact overview on the contribution of mutations in mtDNA to the pathogenesis of diabetes mellitus, with emphasis on the A3243G mutation in the tRNA(Leu, UUR) gene. This mutation associates in most individuals with maternally inherited diabetes and deafness (MIDD) whereas in some other carriers the MELAS syndrome or a progressive kidney failure is seen. Possible pathogenic mechanisms are discussed especially the question why particular mutations in mtDNA associate with distinct clinical entities. Mutations in mtDNA can affect the ATP production, thereby leading to particular clinical phenotypes such as muscle weakness. On the other hand mtDNA mutations may also alter the intracellular concentration of mitochondrial metabolites which can act as signalling molecules, such as Ca or glutamate. This situation may contribute to the development of particular phenotypes that are associated with distinct mtDNA mutations.
本综述简要概述了线粒体DNA（mtDNA）突变对糖尿病发病机制的影响，重点关注tRNA（Leu，UUR）基因中的A3243G突变。在大多数个体中，该突变与母系遗传的糖尿病和耳聋（MIDD）相关，而在其他一些携带者中则会出现线粒体脑肌病伴乳酸血症和卒中样发作（MELAS）综合征或进行性肾衰竭。文中讨论了可能的致病机制，特别是mtDNA中的特定突变为何与不同临床实体相关的问题。mtDNA突变可影响ATP的产生，从而导致特定的临床表型，如肌肉无力。另一方面，mtDNA突变也可能改变线粒体代谢物的细胞内浓度，这些代谢物可作为信号分子，如钙或谷氨酸。这种情况可能有助于与不同mtDNA突变相关的特定表型的发展。
