Regulation of Hepatic PTG Expression by Glucocorticoids

Glucocorticoids increase liver glycogen levels, but the mechanism and relevance of this process are unknown. By unbiased analyses of multiple transcriptomes using the NURSA platform we have identified PTG, a glycogen-associated protein phosphatase targeting subunit as a novel, glucocorticoid-induced protein. The objective of this proposal is to characterize the nature and relevance of GR/glucocorticoid-dependent induction of PTG expression. To do this we propose to first identify the mechanism by which glucocorticoids result in increased PTG expression, including identification of regulatory elements in the PTG promoter. Second, using PTG knockout mice, we propose to evaluate the relevance of glucocorticoid-dependent induction of PTG on glucose homeostasis. Together these aims will validate a novel nuclear hormone receptor target and establish its relevance in the endocrine control of glucose metabolism.