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

对线粒体DNA 3243碱基突变(mt DNA 3243突变)的糖尿病患者的胰岛进行了原位研究，检测了线粒体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。胰腺细胞色素c氧化酶(COX)和琥珀酸脱氢酶(SDH)活性进行组织化学染色，仅1例胰腺组织中检测到线粒体DNA3243。对52个胰岛进行了包括COX和SDH在内的线粒体酶染色。1例mtDNA3243突变的IDDM患者的胰岛全部缺乏COX酶活性，而13例IDDM患者、10例NIDDM患者和10例非糖尿病患者的胰岛COX活性均为阳性。线粒体DNA3243突变的胰岛SDH活性全部为阳性，而无突变的IDDM、NIDDM和非糖尿病患者的胰岛SDH活性较弱。1例mtDNA3243突变患者表现为胰腺淀粉样变。结论：mtDNA3243突变的IDDM患者胰岛β细胞体积显著缩小，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.