Imperial College London
Alternate

DrDavidHodson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Senior Lecturer (non-clinical)
 
 
 
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Contact

 

+44 (0)20 7594 1713d.hodson Website

 
 
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Location

 

329ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Viloria:2019:10.1101/2019.12.19.881185,
author = {Viloria, K and Nasteska, D and Briant, LJB and Heising, S and Larner, D and Fine, NHF and Ashford, FB and Silva, Xavier GD and Ramos, MJ and Manning, Fox JE and MacDonald, PE and Akerman, I and Lavery, GG and Flaxman, C and Morgan, NG and Richardson, SJ and Hewison, M and Hodson, DJ},
doi = {10.1101/2019.12.19.881185},
title = {Vitamin D-binding protein is required for the maintenance of α-cell function and glucagon secretion},
url = {http://dx.doi.org/10.1101/2019.12.19.881185},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>ABSTRACT</jats:title><jats:p>Vitamin D-binding protein (DBP) or GC-globulin carries vitamin D metabolites from the circulation to target tissues. DBP expression is highly-localized to the liver and pancreatic α-cells. While DBP serum levels, gene polymorphisms and autoantigens have all been associated with diabetes risk, the underlying mechanisms remain unknown. Here, we show that DBP regulates α-cell morphology, α-cell function and glucagon secretion. Deletion of DBP led to smaller and hyperplastic α-cells, altered Na<jats:sup>+</jats:sup>channel conductance, impaired α-cell activation by low glucose, and reduced rates of glucagon secretion. Mechanistically, this involved reversible changes in islet microfilament abundance and density, as well as changes in glucagon granule distribution. Defects were also seen in β-cell and δ-cell function. Immunostaining of human pancreata revealed generalized loss of DBP expression as a feature of late-onset and longstanding, but not early-onset type 1 diabetes. Thus, DBP is a critical regulator of α-cell phenotype, with implications for diabetes pathogenesis.</jats:p><jats:sec><jats:title>HIGHLIGHTS</jats:title><jats:p><jats:list list-type="bullet"><jats:list-item><jats:p>DBP expression is highly-localized to mouse and human α-cells</jats:p></jats:list-item><jats:list-item><jats:p>Loss of DBP increases α-cell number, but decreases α-cell size</jats:p></jats:list-item><jats:list-item><jats:p>α-cells in DBP knockout islets are dysfunctional and secrete less glucagon</jats:p></jats:list-item><jats:list-item><jats:p>DBP expression is decreased in α-cells of donors with late-onset or longstanding type 1 diabetes</jats:p></jats:list-item></jats:list></jats:p></jat
AU  - Viloria,K
AU  - Nasteska,D
AU  - Briant,LJB
AU  - Heising,S
AU  - Larner,D
AU  - Fine,NHF
AU  - Ashford,FB
AU  - Silva,Xavier GD
AU  - Ramos,MJ
AU  - Manning,Fox JE
AU  - MacDonald,PE
AU  - Akerman,I
AU  - Lavery,GG
AU  - Flaxman,C
AU  - Morgan,NG
AU  - Richardson,SJ
AU  - Hewison,M
AU  - Hodson,DJ
DO  - 10.1101/2019.12.19.881185
PY  - 2019///
TI  - Vitamin D-binding protein is required for the maintenance of α-cell function and glucagon secretion
UR  - http://dx.doi.org/10.1101/2019.12.19.881185
ER  -
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