The Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis.


Journal Article

The prohormone VGF is expressed in neuroendocrine and endocrine tissues and regulates nutrient and energy status both centrally and peripherally. We and others have shown that VGF-derived peptides have direct action on the islet β cell as secretagogues and cytoprotective agents; however, the endogenous function of VGF in the β cell has not been described. Here, we demonstrate that VGF regulates secretory granule formation. VGF loss-of-function studies in both isolated islets and conditional knockout mice reveal a profound decrease in stimulus-coupled insulin secretion. Moreover, VGF is necessary to facilitate efficient exit of granule cargo from the trans-Golgi network and proinsulin processing. It also functions to replenish insulin granule stores following nutrient stimulation. Our data support a model in which VGF operates at a critical node of granule biogenesis in the islet β cell to coordinate insulin biosynthesis with β cell secretory capacity.

Full Text

Duke Authors

Cited Authors

  • Stephens, SB; Edwards, RJ; Sadahiro, M; Lin, W-J; Jiang, C; Salton, SR; Newgard, CB

Published Date

  • September 2017

Published In

Volume / Issue

  • 20 / 10

Start / End Page

  • 2480 - 2489

PubMed ID

  • 28877479

Pubmed Central ID

  • 28877479

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

International Standard Serial Number (ISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2017.08.050


  • eng