Glucagon regulates gluconeogenesis through KAT2B- and WDR5-mediated epigenetic effects.

ABSTRACT: Circulating pancreatic glucagon is increased during fasting and maintains glucose balance by stimulating hepatic gluconeogenesis. Glucagon triggering of the cAMP pathway upregulates the gluconeogenic program through the phosphorylation of cAMP response element-binding protein (CREB) and the dephosphorylation of the CREB coactivator CRTC2. Hormonal and nutrient signals are also thought to modulate gluconeogenic gene expression by promoting epigenetic changes that facilitate assembly of the transcriptional machinery. However, the nature of these modifications is unclear. Using mouse models and in vitro assays, we show that histone H3 acetylation at Lys 9 (H3K9Ac) was elevated over gluconeogenic genes and contributed to increased hepatic glucose production during fasting and in diabetes. Deph

SUBMITTER: Ravnskjaer K 

PROVIDER: S-EPMC3784539 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature