Adenosine diphosphate and calcium stimulation of respiration in mitochondria from alloxan diabetic rats

Liver mitochondria from normal and alloxan diabetic rats, isolated in 0.25 M sucrose, were assayed with an oxygen electrode for ADP/O and Ca +2 /O ratios, respiratory ratio, and respiratory control index. Mitochondria were incubated with two substrates, succinate and β‐hydroxybutyrate; two types of ionic media, Na + medium (Na + the major monovalent cation) and K + medium (K + the major monovalent cation); and two respiratory stimulants, ADP (352 μM) and Ca +2 (187 μM). Significant differences between respiratory rates and ADP/O ratios were dependent upon the substrate and ionic medium employed. The results confirm previous studies which showed no alteration in ADP/O ratio but decreased State 3 respiratory rates under similar conditions of K + medium with ADP stimulation in the diabetic. Furthermore, the State 3 respiration was prolonged compared to normal. Ca +2 stimulation was the same in normal and diabetic mitochondria in K + medium. Studies in Na + media revealed more significant differences in RCI's, respiratory rates, and ADP/O ratios that were substrate dependent as well as ion dependent. The results from these various studies can be accounted for by an hypothesis linking mitochondrial K + interaction with alterations in the diabetic mitochondria.