Pyruvate dehydrogenase activity in cardiac mitochondria from genetically diabetic mice

Pyruvate dehydrogenase (PDH) was studied in isolated heart mitochondria from genetically diabetic mice (C57BL/KsJ db/db) with progressive cardiomyopathy. Both the basal activity (active enzyme) and the total activity (the sum of active and inactive enzyme) were determined. In mitochondrial extracts from 8-18-wk-old db/db mice, there was a 73% decrease of basal activity accompanied by a 38% decrease of total activity as compared with controls. The lower basal activity at 8 wk of age suggests an increased conversion of the enzyme into the phosphorylated (inactive) form. Evidence is also given that the conversion of inactive (phosphorylated) enzyme into active (dephosphorylated) enzyme is inhibited in cardiac mitochondria prepared from 8-wk and older db/db mice. These changes coincide with the onset of defective oxidative metabolism and can explain the depressed pyruvate oxidation reported previously.