Novel Mechanism of Foxo1 Phosphorylation in Glucagon Signaling in Control of Glucose Homeostasis.

ABSTRACT: Dysregulation of hepatic glucose production (HGP) serves as a major underlying mechanism for the pathogenesis of type 2 diabetes. The pancreatic hormone glucagon increases and insulin suppresses HGP, controlling blood glucose homeostasis. The forkhead transcription factor Foxo1 promotes HGP through increasing expression of genes encoding the rate-limiting enzymes responsible for gluconeogenesis. We previously established that insulin suppresses Foxo1 by Akt-mediated phosphorylation of Foxo1 at Ser²⁵⁶ in human hepatocytes. In this study, we found a novel Foxo1 regulatory mechanism by glucagon, which promotes Foxo1 nuclear translocation and stability via cAMP- and protein kinase A-dependent phosphorylation of Foxo1 at Ser²⁷⁶ Replacing Foxo1-S276 with alanine (A) or aspa

SUBMITTER: Wu Y 

PROVIDER: S-EPMC6198346 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature