Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis.

ABSTRACT: Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c

SUBMITTER: Wang H 

PROVIDER: S-EPMC5007496 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature