STARVATION AND DIABETES INCREASE THE AMOUNT OF PYRUVATE-DEHYDROGENASEKINASE ISOENZYME-4 IN RAT-HEART

This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been sta rved or rendered diabetic with streptozotocin. Re-feeding of starved r ats and insulin treatment of diabetic rats very effectively reversed t he increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats, Starvation and diabetes also markedly incre ased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls, In contrast with th e findings for PDK4, little or no changes in the amounts of PDK1 and P DK2 protein and the abundance of their messages occurred In response t o starvation and diabetes. The observed shift in the relative abundanc e of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulati on of the activity of the pyruvate dehydrogenase complex in rat heart.