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

Samuel B. Stephens, Robert J. Edwards, Masato Sadahiro, Wei Jye Lin, Cheng Jiang, Stephen R. Salton, Christopher B. Newgard

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2480-2489
Number of pages10
JournalCell Reports
Volume20
Issue number10
DOIs
StatePublished - 5 Sep 2017

Keywords

  • VGF
  • chromogranin B
  • granule biogenesis
  • insulin secretion
  • secretory granule
  • β cell function

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