The Prohormone VGF Regulates beta 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

doi:10.1016/j.celrep.2017.08.050

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

Journal article

Open access

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

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

Cell reports (Cambridge), Vol.20(10), pp.2480-2489

09/05/2017

DOI: 10.1016/j.celrep.2017.08.050

PMCID: PMC5624795

PMID: 28877479

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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 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.

Cell Biology

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: The Prohormone VGF Regulates beta Cell Function via Insulin Secretory Granule Biogenesis
Creators: Samuel B. Stephens - Duke University
Robert J. Edwards - Duke University
Masato Sadahiro - Icahn School of Medicine at Mount Sinai
Wei-Jye Lin - Icahn School of Medicine at Mount Sinai
Cheng Jiang - Icahn School of Medicine at Mount Sinai
Stephen R. Salton - Allen Institute for Brain Science
Christopher B. Newgard - Duke University
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.20(10), pp.2480-2489
DOI: 10.1016/j.celrep.2017.08.050
PMID: 28877479
PMCID: PMC5624795
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: Elsevier
Number of pages: 10
Grant note: R01DE021996 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) DK099294; DK046492; DK071308; DE021996; MH086499 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01DK046492 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Eli Lilly R01MH086499 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) Diabetes Action Research and Education Foundation
Language: English
Date published: 09/05/2017
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984359957502771

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