Starvation increases the amount of pyruvate dehydrogenase kinase in several mammalian tissues

Covalent modification of the pyruvate dehydrogenase complex provides an imp ortant regulatory mechanism for controlling the disposal of glucose and oth er compounds metabolized to pyruvate. Regulation of the complex by this mec hanism is achieved in part by tissue-specific expression of the genes encod ing isoenzymes of pyruvate dehydrogenase kinase (PDK), Starvation is known from our previous work to increase PDK activity of heart and skeletal muscl e by increasing the amount of PDK isoenzyme 4 (PDK4) present in these tissu es. This study demonstrates that increased expression of both PDK4 and PDK2 occurs in rat liver, kidney, and lactating mammary gland in response to st arvation. PDK4 and PDK2 message levels were also increased by starvation in the two tissues examined (liver and kidney), suggesting enhancement of gen e transcription. Changes in PDK2 message and protein were of similar magnit ude, but changes in PDK4 message were greater than those in PDK4 protein, s uggesting regulation at the level of translation. In contrast to these tiss ues, starvation had little or no effect on PDK2 and PDK4 protein in brain, white adipose tissue, and brown adipose tissue. Nevertheless, PDK4 message levels were significantly increased in brain and white adipose tissue by st arvation. The findings of this study indicate that increased expression of PDK isoenzymes is an. important mechanism for bringing about inactivation o f the pyruvate dehydrogenase complex during starvation in many but not all tissues of the body. The absence of this mechanism preserves the capacity o f neuronal tissue to utilize glucose for energy during starvation. (C) 2000 Academic Press.