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Diabetes 52:1371-1376, 2003
© 2003 by the American Diabetes Association, Inc.

Starvation and Diabetes Reduce the Amount of Pyruvate Dehydrogenase Phosphatase in Rat Heart and Kidney

Boli Huang1, Pengfei Wu1, Kirill M. Popov2, and Robert A. Harris, 1

1 Department of Biochemistry and Molecular Biology, Indiana University and the School of Medicine, Indianapolis, Indiana
2 Division of Molecular Biology and Biochemistry, University of Missouri-Kansas City, Kansas City, Missouri

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 Ca2+-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 Ca2+-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.



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