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Am J Physiol Endocrinol Metab 297: E578-E591, 2009. First published June 16, 2009; doi:10.1152/ajpendo.00093.2009
0193-1849/09 $8.00
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REVIEWS

The Randle cycle revisited: a new head for an old hat

Louis Hue1 and Heinrich Taegtmeyer2

1Université Catholique de Louvain and de Duve Institute, Hormone and Metabolic Research Unit, Brussels, Belgium; and 2University of Texas Medical School at Houston, Department of Internal Medicine, Division of Cardiology, Houston, Texas

Submitted 11 February 2009 ; accepted in final form 11 June 2009

ABSTRACT

In 1963, Lancet published a paper by Randle et al. that proposed a "glucose-fatty acid cycle" to describe fuel flux between and fuel selection by tissues. The original biochemical mechanism explained the inhibition of glucose oxidation by fatty acids. Since then, the principle has been confirmed by many investigators. At the same time, many new mechanisms controlling the utilization of glucose and fatty acids have been discovered. Here, we review the known short- and long-term mechanisms involved in the control of glucose and fatty acid utilization at the cytoplasmic and mitochondrial level in mammalian muscle and liver under normal and pathophysiological conditions. They include allosteric control, reversible phosphorylation, and the expression of key enzymes. However, the complexity is formidable. We suggest that not all chapters of the Randle cycle have been written.

adenosine 5'-monophosphate-activated protein kinase; fatty acids; glucose; heart; insulin resistance; liver; mitochondria; peroxisome proliferator-activated receptor; skeletal muscle; type 2 diabetes


Address for reprint requests and other correspondence: L. Hue, HORM unit, UCL 7529, Ave. Hippocrate, 75, B-1200 Brussels, Belgium (e-mail address: louis.hue{at}uclouvain.be)






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