Figure 2.
Glucagon requires InsP3-mediated intrahepatic lipolysis to promote VPC and HGP. (a) ATGL S406 phosphorylation (n=5). Blots in Figures 1f and 2a, and Extended Data Figures 1b, 1d, 1f, 5f, 5g, and 7a were stripped and re-probed for all proteins of interest. (b) Glucose production in hepatocytes (n=6 mice per group) incubated in the ATGL inhibitor atglistatin and/or glucagon. ****P<0.0001 vs. WT-glucagon-atglistatin, §§§§ vs. WT+gluagon-atglistatin. (c)-(d) Plasma glucose and insulin concentrations in mice treated with an adeno-associated virus to knock down ATGL in a liver-specific manner. In panels (c)-(h), n=6 WT, 5 WT+ATGL knockdown, 6 KO±ATGL knockdown). (e)-(f) Liver long-chain- and acetyl-CoA concentrations following a 2 hr glucagon infusion. (g)-(h) Hepatic glucose production and hepatic VPC. In all panels, the mean±S.E.M. is shown. Groups were compared before and after glucagon (panels c and d) by the 2-tailed paired Student’s t-test, and groups in all other panels (as well as the four separate groups in panels c and d) were compared by the 2-tailed unpaired Student’s t-test.