Imperial College London
Alternate

ProfessorGuyRutter

Faculty of Medicine, Department of Medicine

Visiting Professor
 
 
 
//

Contact

 

+44 (0)20 7594 3340g.rutter Website

 
 
//

Location

 

ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Kleiner:2018:10.1073/pnas.1721418115,
author = {Kleiner, S and Gomez, D and Megra, B and Na, E and Bhavsar, R and Xin, Y and Rojas, J and Dominiguez-Gutierrez, G and Zanbrowicz, B and Carrat, G and Chabosseau, P and Hu, M and Murphy, AJ and Yancopoulos, GD and Rutter, GA and Gromada, J},
doi = {10.1073/pnas.1721418115},
journal = {Proceedings of the National Academy of Sciences},
pages = {E7642--E7649},
title = {Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity},
url = {http://dx.doi.org/10.1073/pnas.1721418115},
volume = {115},
year = {2018}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - SLC30A8 encodes a zinc transporter that is primarily expressed in the pancreatic islets of Langerhans. In β-cells it transports zinc into insulin-containing secretory granules. Loss-of-function (LOF) mutations in SLC30A8 protect against type 2 diabetes in humans. In this study, we generated a knockin mouse model carrying one of the most common human LOF mutations for SLC30A8, R138X. The R138X mice had normal body weight, glucose tolerance, and pancreatic β-cell mass. Interestingly, in hyperglycemic conditions induced by the insulin receptor antagonist S961, the R138X mice showed a 50% increase in insulin secretion. This effect was not associated with enhanced β-cell proliferation or mass. Our data suggest that the SLC30A8 R138X LOF mutation may exert beneficial effects on glucose metabolism by increasing the capacity of β-cells to secrete insulin under hyperglycemic conditions.
AU  - Kleiner,S
AU  - Gomez,D
AU  - Megra,B
AU  - Na,E
AU  - Bhavsar,R
AU  - Xin,Y
AU  - Rojas,J
AU  - Dominiguez-Gutierrez,G
AU  - Zanbrowicz,B
AU  - Carrat,G
AU  - Chabosseau,P
AU  - Hu,M
AU  - Murphy,AJ
AU  - Yancopoulos,GD
AU  - Rutter,GA
AU  - Gromada,J
DO  - 10.1073/pnas.1721418115
EP  - 7649
PY  - 2018///
SN  - 0027-8424
SP  - 7642
TI  - Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity
T2  - Proceedings of the National Academy of Sciences
UR  - http://dx.doi.org/10.1073/pnas.1721418115
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30038024
UR  - https://www.pnas.org/content/115/32/E7642
UR  - http://hdl.handle.net/10044/1/62724
VL  - 115
ER  -
Download