Glucagon Phosphorylates Serine 552 of β-catenin Leading to Increased Expression of Cyclin D1 and c-Myc in the Isolated Rat Liver

Arch Physiol Biochem. 2015;121(3):88-96. doi: 10.3109/13813455.2015.1048693. Epub 2015 Jul 1.

Abstract

In the last 20 years the prevalence of metabolic disorders, in particular type 2 diabetes (T2D), has more than doubled. Recently, a strong link between T2D and cancer, in particularly liver cancer has been reported. However, the mechanism connecting the development of type 2 diabetes and cancer remains unknown. One of the biggest drivers of liver cancer is alterations in the Wnt/β-catenin pathway. In this study, we aimed to identify the effect of glucagon on β-catenin in the isolated rat liver. We found glucagon, which is substantially raised in patients with T2D, rapidly phosphorylates β-catenin on serine 552 that is associated with increased expression of genes cyclin D1 (CCND1) and c-Myc (MYC), which are known to be involved in liver cancer. This finding may explain the increased risk of liver cancer in people with T2D.

Keywords: T2D; cancer; glucagon; β-Catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin D1 / agonists
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Gene Expression Regulation
  • Glucagon / metabolism
  • Glucagon / pharmacology*
  • Infusion Pumps
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Organ Culture Techniques
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-myc / agonists
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serine / metabolism*
  • Wnt Signaling Pathway
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Ccnd1 protein, rat
  • Ctnnb1 protein, rat
  • Proto-Oncogene Proteins c-myc
  • beta Catenin
  • Cyclin D1
  • Serine
  • Glucagon