A study of respiration and oxidative phosphorylation of mitochondria from regenerating liver of normal and diabetic rats.

Summary Mitochondria from regenerating liver of normal and alloxan-diabetic rats were assayed polarographically for respiratory rate and oxidative phosphorylation. Approximately 65 to 70% of the liver was removed by a simple surgical procedure, and the animals were sacrificed at different intervals from 16 hr to 4 weeks after partial hepatectomy. Mitochondria were isolated in a sucrose/tris(hydroxymethyl)-aminomethane/ethylenediaminetetracetate medium and incubated with two respiratory substrates, succinate and β-hydroxybutyrate. Significant changes in the rate of respiration and the efficiency of oxidative phosphorylation were observed in the mitochondria from regenerating livers of both normal and diabetic rats. Respiratory control ratios and State 3 respiratory rates were increased during the regeneration period with the greatest increase observed in the groups studied at 24 hours, 72 hours, and 2 weeks after partial hepatectomy in both normal and diabetic rats. Adenosine diphosphate/oxygen ratios were also elevated, indicating an increased efficiency of adenosine triphosphate formation in mitochondria from regenerating liver. With succinate as a respiratory substrate, there was a cyclical increase in mitochondrial respiratory activity, while with β-hydroxybutyrate there was a greater proportional elevation which was sustained. The respiratory activity of diabetic control mitochondria was lower than in the normal control, but it was markedly increased during the regenerating period. Consequently, the percentage of increase of mitochondrial respiratory activity in regenerating liver of diabetic rats was much higher than that observed in normal regenerating groups. The data indicate tightly coupled oxidative phosphorylation and increased efficiency in mitochondria from regenerating liver in both normal and diabetic rats.