京都大学 / 新制・課程博士 / 博士(農学) / 甲第24110号 / 農博第2515号 / 新制||農||1093(附属図書館) / 学位論文||R4||N5401(農学部図書室) / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 井上 和生, 教授 谷 史人, 准教授 後藤 剛 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Mitochondria are found in all cells of the body except red blood cells. Mitochondria is the organelle that produces the most ATP in the body, which is the cells energy carrier. All processes in the body require energy in one way or another, hence the function of mitochondria is very important. In mitochondrial disease, there is an impairment in the function of the mitochondria, where the respiration usually is affected. Mitochondria play a big role in the regulation of glucose-stimulated insulin secretion of the pancreatic β-cells hence why diabetes often can be caused by mitochondrial dysfunction. Diabetes often requires treatment to achieve normal blood sugar levels. Metformin, rosiglitazone and troglitazone are three drugs for treatment of type 2 diabetes and have been proven to affect mitochondrial function or the body negatively, hence why it is important to be careful with which treatment that is used in case of mitochondrial diabetes. The purpose of this ex vivo model with human mitochondria were to investigate with high resolution respirometry whether the antidiabetic drugs could reduce the respiration in mitochondria and at what concentration it became significant. The results showed that metformin did not decrease the respiration at all with additions in the range of 10 µM to 100 µM, which rosiglitazone and troglitazone did. The therapeutic concentrations of the drugs are lower than the concentrations investigated in this study. However, since healthy cells are used in this study the effect that the drugs have on impaired mitochondria could be different. The conclusion of this study is that there was a significant decrease in the respiration for two of three drugs and should be carefully used. Further studies with impaired mitochondria should be performed to really see what affect these drugs have.