The
pyruvate dehydrogenase complex (PDC) is inactivated in many tissues during
starvation and diabetes to conserve three-
carbon compounds for gluconeogenesis. This is achieved by an increase in the extent of PDC phosphorylation caused in part by increased
pyruvate dehydrogenase kinase (PDK) activity due to increased PDK expression. This study examined whether altered
pyruvate dehydrogenase phosphatase (PDP) expression also contributes to changes in the phosphorylation state of PDC during
starvation and diabetes. Of the two PDP
isoforms expressed in mammalian tissues, the Ca(2+)-sensitive
isoform (PDP1) is highly expressed in rat heart, brain, and testis and is detectable but less abundant in rat muscle, lung, kidney, liver, and spleen. The Ca(2+)-insensitive
isoform (PDP2) is abundant in rat kidney, liver, heart, and brain and is detectable in spleen and lung.
Starvation and
streptozotocin-induced diabetes cause decreases in PDP2
mRNA abundance, PDP2
protein amount, and PDP activity in rat heart and kidney. Refeeding and
insulin treatment effectively reversed these effects of
starvation and diabetes, respectively. These findings indicate that opposite changes in expression of specific PDK and PDP
isoenzymes contribute to hyperphosphorylation and therefore inactivation of the PDC in heart and kidney during
starvation and diabetes.