title: Dual role of VAMP8 in regulating insulin exocytosis and islet β cell growth.
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.
authors: Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors: Dan
authors: D
authors: Zhu
authors: Yi
authors: Y
authors: Zhang
authors: Patrick P L
authors: PP
authors: Lam
authors: Subhankar
authors: S
authors: Dolai
authors: Yunfeng
authors: Y
authors: Liu
authors: Erica P
authors: EP
authors: Cai
authors: Diana
authors: D
authors: Choi
authors: Stephanie A
authors: SA
authors: Schroer
authors: Youhou
authors: Y
authors: Kang
authors: Emma M
authors: EM
authors: Allister
authors: Tairan
authors: T
authors: Qin
authors: Michael B
authors: MB
authors: Wheeler
authors: Cheng-Chun
authors: CC
authors: Wang
authors: Wan-Jin
authors: WJ
authors: Hong
authors: Minna
authors: M
authors: Woo
authors: Herbert Y
authors: HY
authors: Gaisano
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005089:Exocytosis / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism* / Q000627:therapeutic use; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018408:Patch-Clamp Techniques; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D050683:R-SNARE Proteins; C491831:Vamp8 protein, mouse; D052216:Glucagon-Like Peptide 1