isoenzyme4expression.PDFVIP

Biochem. J. (2000) 346, 651–657 (Printed in Great Britain) 651 Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression Mary C. SUGDEN*1, Alexandra KRAUS*, Robert A. HARRIS? and Mark J. HOLNESS* *Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, St Bartholomew’s and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London E1 4NS, U.K., and ?Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202–5122, U.S.A. Using immunoblot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoenzymes PDK2 and PDK4, we demonstrate selective changes in PDK isoenzyme expression in slow-twitch versus fast-twitch skeletal muscle types in response to prolonged (48 h) starvation and refeeding after starvation. Starvation increased PDK activity in both slow-twitch (soleus) and fast-twitch (anterior tibialis) skeletal muscle and was associated with loss of sensitivity of PDK to inhibition by pyruvate, with a greater effect in anterior tibialis. Starvation significantly increased PDK4 protein ex- pression in both soleus and anterior tibialis, with a greater response in anterior tibialis. Starvation did not effect PDK2 pro- tein expression in soleus, but modestly increased PDK2 expression in anterior tibialis. Refeeding for 4 h partially reversed the effect of 48-h starvation on PDK activity and PDK4 expression in both soleus and anterior tibialis, but the response was more marked in soleus than in anterior tibialis. Pyruvate sensitivity of PDK activity was also partially restored by re- INTRODUCTION Regulation of the activity of the pyruvate dehydrogenase complex (PDC) is an important component of the regulation of glucose homeostasis.