title: 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.
authors.affiliation: Department of Pharmacology , UNSW Australia, NSW , Australia and.
authors.forename: Md Kamrul H
authors.initials: MK
authors.lastname: Chowdhury
authors.forename: Magda K
authors.initials: MK
authors.lastname: Montgomery
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cognard
authors.forename: Peter R
authors.initials: PR
authors.lastname: Shepherd
authors.forename: Greg C
authors.initials: GC
authors.lastname: Smith
mesh_terms: D000818:Animals; D019938:Cyclin D1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D007260:Infusion Pumps; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C530106:Ccnd1 protein, rat; C495268:Ctnnb1 protein, rat; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; D019938:Cyclin D1; D012694:Serine; D005934:Glucagon
keywords: T2D; cancer; glucagon; β-Catenin