No description available.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13194号 / 論医博第2158号 / 新制||医||1030(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 柳田 素子, 教授 横出 正之, 教授 川口 義弥 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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.