Is there a role for pyruvate dehydrogenase-phosphatase in the re-activation of hepatic pyruvate dehydrogenase complex after re-feeding?

In starvation, inhibition of the pyruvate dehydrogenase complex (PDH) is associated with activation of PDH kinase secondary to increased fat oxidation through increased mitochondrial acetyl-CoA/CoA and N A D H / N A D + concentration ratios (for review, see Randle, 1986). However, acute inhibition of mitochondria1 fat oxidation by 2-tetradecylglycidate ( T D G ) does not lead to reactivation of hepatic PDH in starved rats (Caterson et al., 1982), implying that the assumed fall in acetyl-CoA/CoA and N A D H / N A D + ratios and resultant inhibition of PDH kinase is not sufficient in itself to permit reactivation. Similarly, hepatic PDH re-activation is not observed in starved rats after the administration of dichloroacetate (DCA), a pyruvate analogue which inhibits PDH kinase directly (Holness & Sugden, 1987). Because of the failure to reactivate hepatic PDH by inhibition of PDH kinasc, we speculated that activation of PDH phosphatase might additionally be necessary (Holness & Sugden. 1087). possibly by insulin which has been demonstrated to increase PDH activity via increased PDH phosphatasc activity in adipose tissue (Marshall et al., 1984; Thomas & Denton, 1986). In liver, the effects of insulin on PDH have been inconsistent. Increased hepatic PDH activities have been observed after the injection o f a supraphysiological dose of insulin