Glucagon phosphorylates serine 552 of β-catenin leading to increased expression of cyclin D1 and c-Myc in the isolated rat liver

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.

• β-Catenin
• cancer
• glucagon
• T2D

Acknowledgements

Financial support: This work was supported by the University of New South Wales (UNSW) Australia, PhD stipend (UIPA) of Md. Kamrul Hasan Chowdhury.

Declaration of interest

The authors declare no conflicts of interest.