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

对线粒体DNA 3243碱基对突变（mt DNA 3243突变）的糖尿病患者的胰岛进行了原位鉴定。在本研究中，我们检测了mt DNA 3243突变的糖尿病患者胰岛的β细胞体积和线粒体酶活性。受试者共34个胰腺，其中NIDDM患者10个，IDDM患者14个，非糖尿病患者10个。用组织化学方法检测胰腺细胞色素c氧化酶（COX）和琥珀酸脱氢酶（SDH）活性。34例胰腺中仅1例检测到mtDNA 3243。本例胰腺β细胞体积减小至0.22 g。对52个胰岛进行线粒体酶染色，包括COX和SDH。1例mtDNA 3243突变的IDDM患者的所有胰岛均缺乏COX酶活性，而13例IDDM患者、10例NIDDM患者和10例非糖尿病患者的其他胰岛均有COX酶活性阳性。mtDNA 3243突变患者的胰岛SDH酶活性均呈阳性，而IDDM、NIDDM和非糖尿病患者的胰岛SDH酶活性较弱，而非mtDNA 3243突变患者的胰岛SDH酶活性较弱。胰腺淀粉样蛋白表现为一例mtDNA 3243。总之，在mtDNA 3243突变的IDDM患者中，β细胞体积明显减少，线粒体DNA编码酶（COX）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.