Organ-specific affects of diabetes on mitochondrial function

Increased production of reactive oxygen species (ROS), especially by the mitochondria, is considered to be a central mechanism underlying the development of late diabetic complications. This study aims to determine how mitochondrial functions are changed in different organs during diabetes in order to determine if mitochondrial ROS production effects the development of diabetic complications.

Mitochondria were isolated from hearts, kidneys, and livers of diabetic and control mice. Purity of the isolated mitochondria was checked by FACS. Oxygen consumption, ROS production, and enzyme activity measurements were performed using fluorescence-photometric and spectrophotometric assays. Genexpression profiles were analyzed using qPCR and western blot.

In diabetic animals oxygen consumption was decreased in the hearts and increased in the kidneys and livers. ROS production was decreased in the hearts and increased in the kidneys and livers. The activities of complex I, III and IV of the electron transport chain were changed in the kidneys and livers, complex II and V activities remained unchanged. The expression of complexes II, III, and V was decreased in the kidneys, but not in the hearts or livers. The change in the expression profile of antioxidative enzymes was different in all diabetic organs with the kidneys showing the strongest decrease.

This study shows that diabetes has a differential affect on mitochondrial function depending on the tissue in which the kidney was found to be worst affected. This would suggest that mitochondrial properties of organs which are highly susceptible to chronic hyperglycemia are likely to be the more affected during diabetes.