Abstract

Article info 2014 2 (4)    002  (04)   pp.  135 ~ 141
Title Role of CRTC2 in the control of hepaticgluconeogenesis
Authors Hye-Sook Han and Seung-Hoi Koo
Institutions Division of Life Sciences, College of Life Sciences & Biotechnology, Korea University, Seoul 136-713, Korea. *Correspondence: koohoi@korea.ac.kr
Abstract Fasting glucose metabolism in the liver is critical in maintaining energy homeostasis in mammals. To provide sufficient amounts of glucose in the bloodstream, a preferred fuel for most tissues, glucose production from the liver is activated under starvation conditions. Short-term fasting elicits the production of glucose from glycogen, a storage form of glucose in the liver, by activating glycogenolysis. Longer-term fasting or starvation also triggers the activation of de novo glucose synthesis, or gluconeogenesis, by utilizing various precursors such as lactate, amino acids, or glycerol. Activation of the latter pathway is achieved mainly via transcriptional mechanism, and fasting hormone glucagon or stress hormone epinephrine induces cAMP-dependent pathway in the liver, thus activating transcription factor cAMP response element binding protein (CREB) and the resultant transcription of downstream target genes in the gluconeogenesis including phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase catalytic subunit (G6Pase). While CREBdependent transcriptional pathway is activated under fasting conditions, feeding effectively reduces glucose production from the liver in part by reducing CREB-dependent transcriptional activation of gluconeogenic gene expression. Increased hepatic glucose production under insulin resistance or type 2 diabetes is an important underlying mechanism for hyperglycemia, and it was shown that hyperactivation of CREB-dependent transcription can be attributable for such phenomenon. In this review, we would like to delineate the mechanistic insight into the role of CREB regulated transcription coactivator 2 (CRTC2), a new transcriptional coactivator of CREB, in the control of hepatic gluconeogenesis.