인슐린비의존성 당뇨병 동물모델에서 미토콘드리아 DNA 보제수의 감소 = Devrease of Mitochondrial DNA Content in Non-Insulin Dependent Diabetic Rats

다국어 초록 (Multilingual Abstract)

Background: Although genetic disorder in diabetes mellitus (DM) is not well understood, it has been suggested that the maternally inherited mitochondrial DNA which does not follow the Mendel's laws is a genetic factor for DM. It was reported that the mitochondrial DNA contents in DM patients were decreased compared to the normal control. Similar decrease in mitochondria) DNA content before DM development was tested in animal models.
Method: The mitochondria) DNA (mtDNA) content in various tissues obtained from two types of non-insulin dependent diabetic rats, Goto-Kakizaki (GK) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats at different ages were quantified. We also determined the quantity of hepatic COX subunit III (COX III) mRNA, and the enzyme activities of succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) in mitochondria isolated from liver and skeletal muscle were measured.
Results: At 6 weeks, mfiDNA content of GK rat liver was 20% decreased compared to the Wistar control, The mtDNA content of Wistar rat liver was decreased to aging from 6 weeks to 24 weeks while mtDNA in GK rat liver remains relatively constant. In case of skeletal muscle, however, mtDNA contents in GK rats were 50% decreased compared to the control at 12 and 24 week old. Similarly, OLETF and LETO control rats showed the age-dependent decrease of mtDNA content in liver and pancreas. Especially the mtDNA contents in OLETF rat tissues were reduced at the younger age than the LETO control content. That is, at 6 weeks old mtDNA contents in OLETF rat pancreas and liver were only 50% of the control. The level of mitochondrial coded hepatic COX subunit III mRNA tends to decrease with age. Despite the decrease of mtDNA content, hepatic COX III mRNA level and COX activities and SDH activities were not altered significantly, implying that the change of mtDNA contents did not damage the mitochondria) gene transcription and mitochondria) function dramatically.
Conclusions: This results suggest that mtDNA contents in pancreas and liver decrease age-depehdently but it occurs at younger age in NIDDM. The decrease of mtDNA content at young age may be a cause of NIDDM.