Dual role of VAMP8 in regulating insulin exocytosis and islet ß cell growth.
Cell Metab
; 16(2): 238-49, 2012 Aug 08.
Article
in En
| MEDLINE
| ID: mdl-22841572
ABSTRACT
Optimal insulin secretion required to maintain glucose homeostasis is the summation of total pancreatic islet ß cell mass and intrinsic secretory capacity of individual ß cells, which are regulated by distinct mechanisms that could be amplified by glucagon-like-peptide-1 (GLP-1). Because of these actions of GLP-1 on islet ß cells, GLP-1 has been deployed to treat diabetes. We employed SNARE protein VAMP8-null mice to demonstrate that VAMP8 mediates insulin granule recruitment to the plasma membrane, which partly accounts for GLP-1 potentiation of glucose-stimulated insulin secretion. VAMP8-null mice also exhibited increased islet ß cell mass from increased ß cell mitosis, with ß cell proliferative activity greatly amplified by GLP-1. Thus, despite the ß cell exocytotic defect, VAMP8-null mice have an increased total insulin secretory capacity, which improved glucose homeostasis. We conclude that these VAMP8-mediated events partly underlie the therapeutic actions of GLP-1 on insulin secretion and ß cell growth.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus
/
Insulin-Secreting Cells
/
Glucagon-Like Peptide 1
/
R-SNARE Proteins
/
Exocytosis
/
Insulin
Limits:
Animals
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2012
Type:
Article
Affiliation country:
Canada