Transcriptional Regulation of Pyruvate Dehydrogenase Kinase.
10.4093/dmj.2012.36.5.328
- Author:
Ji Yun JEONG
1
;
Nam Ho JEOUNG
;
Keun Gyu PARK
;
In Kyu LEE
Author Information
1. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea. leei@knu.ac.kr
- Publication Type:Review
- Keywords:
Insulin resistance;
Pyruvate dehydrogenase kinase;
Receptors, cytoplasmic and nuclear;
Transcriptional regulation
- MeSH:
Adenosine Triphosphate;
Adiponectin;
Blood Glucose;
Epinephrine;
Fasting;
Growth Hormone;
Heart;
Insulin;
Insulin Resistance;
Isoenzymes;
Kidney;
Ligands;
Liver;
Metabolic Diseases;
Muscle, Skeletal;
Oxidoreductases;
Peroxisome Proliferator-Activated Receptors;
Phosphorylation;
Phosphotransferases;
Protein-Serine-Threonine Kinases;
Pyruvate Dehydrogenase Complex;
Pyruvic Acid;
Receptors, Cytoplasmic and Nuclear;
Receptors, Glucocorticoid;
Receptors, Thyroid Hormone;
Starvation;
Thiazolidinediones;
Up-Regulation
- From:Diabetes & Metabolism Journal
2012;36(5):328-335
- CountryRepublic of Korea
- Language:English
-
Abstract:
The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes. Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally regulated still remains unclear. Insulin represses the expression of PDK2 and PDK4 via phosphorylation of FOXO through PI3K/Akt signaling pathway. Several nuclear hormone receptors activated due to fasting or increased fat supply, including peroxisome proliferator-activated receptors, glucocorticoid receptors, estrogen-related receptors, and thyroid hormone receptors, also participate in the up-regulation of PDK2 and PDK4; however, the endogenous ligands that bind those nuclear receptors have not been identified. It has been recently suggested that growth hormone, adiponectin, epinephrine, and rosiglitazone also control the expression of PDK4 in tissue-specific manners. In this review, we discuss several factors involved in the expressional regulation of PDK2 and PDK4, and introduce current studies aimed at providing a better understanding of the molecular mechanisms that underlie the development of metabolic diseases such as diabetes.
