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. |