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

First Author  Stephens SB Year  2017
Journal  Cell Rep Volume  20
Issue  10 Pages  2480-2489
PubMed ID  28877479 Mgi Jnum  J:255237
Mgi Id  MGI:6104050 Doi  10.1016/j.celrep.2017.08.050
Citation  Stephens SB, et al. (2017) The Prohormone VGF Regulates beta Cell Function via Insulin Secretory Granule Biogenesis. Cell Rep 20(10):2480-2489
abstractText  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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