Study on the pathogenetic roles of mutation of mitochondrial DNA at position 3243 on diabetes mellitus

线粒体DNA 3243bp突变的糖尿病患者胰岛的原位研究本研究对线粒体DNA 3243突变的糖尿病患者胰岛β细胞体积和线粒体酶活性进行了检测，共取胰岛34个，其中NIDDM患者10个，IDDM患者14个，非糖尿病患者10例。胰腺组织细胞色素c氧化酶（考克斯）和琥珀酸脱氢酶（SDH）的活性检测结果显示，34例胰腺中仅1例检出线粒体DNA 3243。在这种情况下，胰腺β细胞体积减少至0.22 g。对52个胰岛进行了考克斯和SDH酶染色，发现1例3243突变的IDDM患者胰岛均无考克斯酶活性，而13例IDDM患者、10例NIDDM患者和10例非糖尿病患者胰岛均呈考克斯活性。线粒体DNA3243突变的胰岛SDH活性均为阳性，而非突变的IDDM、NIDDM和非糖尿病患者的胰岛SDH活性较弱。1例线粒体DNA 3243突变的IDDM患者胰岛β细胞体积明显减小，线粒体DNA编码酶（考克斯）活性降低。

In situ characterization of the islet in diabetics with mitochondrial DNA mutation at 3243 base pair (mt DNA 3243 mutation) was carried out.In the present study, the islets in the diabetic patients with mt DNA 3243 mutation were examined in terms of beta cell volume and mitochondrial enzyme activities.Thirty-four pancreata, including 10 pancreata from NIDDM patients, 14 pancreata from IDDM patients, and 10 non-diabetics, were composed of the subjects. Cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) activities of the pancreas were stained histochemically.mtDNA 3243 was detected in only 1 of 34 pancreata. Pancreatic beta cell volume in this case was decrease to 0.22 g. Fifty-two islets were examined in a section stained for mitochondrial enzymes including COX and SDH.All islets of an IDDM case with mtDNA 3243 mutation lacked COX enzyme activity, while other islets from 13 IDDM patients, 10 NIDDM patients and 10 non-diabetics had positive COX activity. All islets in the case with mtDNA 3243 mutation examined for SDH activity showed positive enzyme activity, while there were weak activity in the islet for SDH in IDDM,NIDDM and non-diabetics, who did not have the mutation. Pancreatic amyloid was demonstrated in a case with mtDNA 3243.In conclusion, markedly decreased beta cell volume with diminished activity of mitochondrial DNA encoded-enzyme (COX) was demonstrated in an IDDM patients with mtDNA 3243 mutation.