B-cell translocation gene 2 positively regulates GLP-1-stimulated insulin secretion via induction of PDX-1 in pancreatic beta-cells.
- Author:
Seung Lark HWANG
1
;
Okyun KWON
;
Sun Gyun KIM
;
In Kyu LEE
;
Yong Deuk KIM
Author Information
1. College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. ydkim94@gmail.com
- Publication Type:Original Article
- Keywords:
B-cell translocation gene 2;
glucagon-like peptide-1;
insulin;
pancreatic duodenal homeobox-1
- MeSH:
Animals;
Gene Expression Regulation/drug effects;
Glucagon-Like Peptide 1/*pharmacology;
Homeodomain Proteins/*genetics/metabolism;
Humans;
Immediate-Early Proteins/genetics/*metabolism;
Insulin/genetics/*secretion;
Insulin-Secreting Cells/drug effects/*metabolism;
Male;
Mice;
Mice, Inbred C57BL;
Peptides/pharmacology;
Promoter Regions, Genetic/genetics;
Protein Binding/drug effects/genetics;
Rats;
Trans-Activators/*genetics/metabolism;
Tumor Suppressor Proteins/genetics/*metabolism;
Venoms/pharmacology
- From:Experimental & Molecular Medicine
2013;45(5):e25-
- CountryRepublic of Korea
- Language:English
-
Abstract:
Glucagon-like peptide-1 (GLP-1) is a potent glucoincretin hormone and an important agent for the treatment of type 2 diabetes. Here we demonstrate that B-cell translocation gene 2 (BTG2) is a crucial regulator in GLP-1-induced insulin gene expression and insulin secretion via upregulation of pancreatic duodenal homeobox-1 (PDX-1) in pancreatic beta-cells. GLP-1 treatment significantly increased BTG2, PDX-1 and insulin gene expression in pancreatic beta-cells. Notably, adenovirus-mediated overexpression of BTG2 significantly elevated insulin secretion, as well as insulin and PDX-1 gene expression. Physical interaction studies showed that BTG2 is associated with increased PDX-1 occupancy on the insulin gene promoter via a direct interaction with PDX-1. Exendin-4 (Ex-4), a GLP-1 agonist, and GLP-1 in pancreatic beta-cells increased insulin secretion through the BTG2-PDX-1-insulin pathway, which was blocked by endogenous BTG2 knockdown using a BTG2 small interfering RNA knockdown system. Finally, we revealed that Ex-4 and GLP-1 significantly elevated insulin secretion via upregulation of the BTG2-PDX-1 axis in pancreatic islets, and this phenomenon was abolished by endogenous BTG2 knockdown. Collectively, our current study provides a novel molecular mechanism by which GLP-1 positively regulates insulin gene expression via BTG2, suggesting that BTG2 has a key function in insulin secretion in pancreatic beta-cells.
