Format

Send to

Choose Destination
Cell Metab. 2012 Aug 8;16(2):238-49. doi: 10.1016/j.cmet.2012.07.001. Epub 2012 Jul 26.

Dual role of VAMP8 in regulating insulin exocytosis and islet β cell growth.

Author information

1
Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.

Abstract

Optimal insulin secretion required to maintain glucose homeostasis is the summation of total pancreatic islet β cell mass and intrinsic secretory capacity of individual β 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 β 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 β cell mass from increased β cell mitosis, with β cell proliferative activity greatly amplified by GLP-1. Thus, despite the β 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 β cell growth.

PMID:
22841572
DOI:
10.1016/j.cmet.2012.07.001
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center