Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases
- 1 January 2006
- journal article
- review article
- Published by Taylor & Francis in Archives of Physiology and Biochemistry
- Vol. 112 (3) , 139-149
- https://doi.org/10.1080/13813450600935263
Abstract
The mechanisms that control mammalian pyruvate dehydrogenase complex (PDC) activity include its phosphorylation (inactivation) by a family of pyruvate dehydrogenase kinases (PDKs 1 - 4). Here we review new developments in the regulation of the activities and expression of the PDKs, in particular PDK2 and PDK4, in relation to glucose and lipid homeostasis. This review describes recent advances relating to the acute and long-term modes of regulation of the PDKs, with particular emphasis on the regulatory roles of nuclear receptors including peroxisome proliferator-activated receptor (PPAR) alpha and Liver X receptor (LXR), PPAR gamma coactivator alpha (PGC-1alpha) and insulin, and the impact of changes in PDK activity and expression in glucose and lipid homeostasis. Since PDK4 may assist in lipid clearance when there is an imbalance between lipid delivery and oxidation, it may represent an attractive target for interventions aimed at rectifying abnormal lipid as well as glucose homeostasis in disease states.Keywords
This publication has 99 references indexed in Scilit:
- Free Fatty Acids Produce Insulin Resistance and Activate the Proinflammatory Nuclear Factor-κB Pathway in Rat LiverDiabetes, 2005
- Activation of glucose transport during simulated ischemia in H9c2 cardiac myoblasts is mediated by protein kinase C isoformsLife Sciences, 2005
- Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cellsThe FEBS Journal, 2005
- Pyruvate Dehydrogenase Kinase Isoform 2 Activity Limited and Further Inhibited by Slowing Down the Rate of Dissociation of ADPBiochemistry, 2004
- Pyruvate Dehydrogenase Kinase Isoform 2 Activity Stimulated by Speeding Up the Rate of Dissociation of ADPBiochemistry, 2004
- Cardiac-specific Knock-out of Lipoprotein Lipase Alters Plasma Lipoprotein Triglyceride Metabolism and Cardiac Gene ExpressionJournal of Biological Chemistry, 2004
- Dexamethasone induction of hypertension and diabetes is PPAR-α dependent in LDL receptor–null miceNature Medicine, 2003
- Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC‐1The FASEB Journal, 2002
- Marked Differences between Two Isoforms of Human Pyruvate Dehydrogenase KinaseJournal of Biological Chemistry, 2000
- Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complexBiochemical Journal, 1998