Journal
CELL REPORTS
Volume 20, Issue 10, Pages 2480-2489Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.08.050
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Funding
- NIH [DK099294, DK046492, DK071308, DE021996, MH086499]
- Eli Lilly
- Diabetes Action Research and Education Foundation
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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 beta cell as secretagogues and cytoprotective agents; however, the endogenous function of VGF in the beta 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 beta cell to coordinate insulin biosynthesis with beta cell secretory capacity.
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