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

Publication date: 5 September 2017
Source:Cell Reports, Volume 20, Issue 10
Author(s): Samuel B. Stephens, Robert J. Edwards, Masato Sadahiro, Wei-Jye Lin, Cheng Jiang, Stephen R. Salton, Christopher B. Newgard
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.

Graphical abstract

Teaser

Stephens et al. find that the granin protein, VGF, regulates key aspects of pancreatic islet β cell function. These studies highlight a role for VGF in the maintenance and replenishment of insulin granules during nutrient stimulation by promoting exit of granule cargo from the trans-Golgi network and facilitating granule formation.


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