G_12/13-mediated signaling stimulates hepatic glucose production and has a major impact on whole body glucose homeostasis.

ABSTRACT: Altered hepatic glucose fluxes are critical during the pathogenesis of type 2 diabetes. G protein-coupled receptors represent important regulators of hepatic glucose production. Recent studies have shown that hepatocytes express GPCRs that can couple to G_12/13, a subfamily of heterotrimeric G proteins that has attracted relatively little attention in the past. Here we show, by analyzing several mutant mouse strains, that selective activation of hepatocyte G_12/13 signaling leads to pronounced hyperglycemia and that this effect involves the stimulation of the ROCK1-JNK signaling cascade. Using both mouse and human hepatocytes, we also show that activation of endogenous sphingosine-1-phosphate type 1 receptors strongly promotes glucose release in a G_12/13-depe

SUBMITTER: Pittala S 

PROVIDER: S-EPMC11574106 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature