Sam68 promotes hepatic gluconeogenesis via CRTC2.

ABSTRACT: Hepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68^ΔC) or N-terminal (Sam68^ΔN) domains fails to bin

SUBMITTER: Qiao A 

PROVIDER: S-EPMC8185084 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature