title: Insights into Transcriptional Regulation of Hepatic Glucose Production.
abstract: Maintenance of systemic glucose homeostasis is pivotal in animals because most tissues, especially brain and red blood cells, rely on glucose as the sole energy source. The liver protects the body from hypoglycemia because it possesses two biochemical pathways, namely gluconeogenesis and glycogenolysis which provide glucose during starvation period. Posttranslational regulation by allosteric effectors and/or reversible phosphorylation of the key enzymes involved in these two pathways provide the rapid response for the immediate increase in the enzyme activities to accelerate rates of gluconeogenesis and glycogenolysis, but these mechanisms are insufficient for long-term control. Glucoregulatory hormones can alter the rate of enzyme synthesis at the transcriptional step by modulating the key transcription factors and coactivators, such as CREB/CRTC2, FoxO1, nuclear receptors, C/EBPα, hepatocyte nuclear factors, PGC1α, and CLOCK genes. Precise and well-coordinated regulation of activities of these transcription factors at the right time enables liver to synthesize or suppress glucose production, thus maintaining the proper function of tissues and organs during starvation and feeding cycles. Loss of function mutation or deregulation of these key transcription factors and coactivators can result in the pathophysiological condition, such as type 2 diabetes.
authors: Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors: Komsan
authors: K
authors: Anyamaneeratch
authors: Division of Interdisciplinary, Mahidol University, Bangkok, Thailand.
authors: Pinnara
authors: P
authors: Rojvirat
authors: Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors: Witchuda
authors: W
authors: Sukjoi
authors: Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors: Sarawut
authors: S
authors: Jitrapakdee
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; D056926:CLOCK Proteins; C538943:CLOCK protein, human; D005947:Glucose
keywords: Gluconeogenesis; Glycogen metabolism; Glycogenolysis; Liver; Transcription factors; Transcriptional regulation