HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/E46    most recent 00536.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Jeoung, N. H. Articles by Harris, R. A. PubMed PubMed Citation Articles by Jeoung, N. H. Articles by Harris, R. A.

Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese mice

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and the Research Service, Richard Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana

Submitted 16 August 2007 ; accepted in final form 22 April 2008

The effect of pyruvate dehydrogenase kinase-4 (PDK4) deficiency on glucose homeostasis was studied in mice fed a high-fat diet. Expression of PDK4 was greatly increased in skeletal muscle and diaphragm but not liver and kidney of wild-type mice fed the high-fat diet. Wild-type and PDK4^–/– mice consumed similar amounts of the diet and became equally obese. Insulin resistance developed in both groups. Nevertheless, fasting blood glucose levels were lower, glucose tolerance was slightly improved, and insulin sensitivity was slightly greater in the PDK4^–/– mice compared with wild-type mice. When the mice were killed in the fed state, the actual activity of the pyruvate dehydrogenase complex (PDC) was higher in the skeletal muscle and diaphragm but not in the liver and kidney of PDK4^–/– mice compared with wild-type mice. When the mice were killed after overnight fasting, the actual PDC activity was higher only in the kidney of PDK4^–/– mice compared with wild-type mice. The concentrations of gluconeogenic substrates were lower in the blood of PDK4^–/– mice compared with wild-type mice, consistent with reduced formation in peripheral tissues. Diaphragms isolated from PDK4^–/– mice oxidized glucose faster and fatty acids slower than diaphragms from wild-type mice. Fatty acid oxidation inhibited glucose oxidation by diaphragms from wild-type but not PDK4^–/– mice. NEFA, ketone bodies, and branched-chain amino acids were elevated more in PDK4^–/– mice, consistent with slower rates of oxidation. These findings show that PDK4 deficiency lowers blood glucose and slightly improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity.

pyruvate dehydrogenase kinase-4-knockout mice; diet-induced obesity; glucose oxidation; fatty acid oxidation; branched-chain amino acids

This article has been cited by other articles:

				H. Crossland, D. Constantin-Teodosiu, S. M. Gardiner, D. Constantin, and P. L. Greenhaff A potential role for Akt/FOXO signalling in both protein loss and the impairment of muscle carbohydrate oxidation during sepsis in rodent skeletal muscle J. Physiol., November 15, 2008; 586(22): 5589 - 5600. [Abstract] [Full Text] [PDF]

				M. C. Sugden PDC deletion: the way to a man's heart disease Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H917 - H919. [Full Text] [PDF]