Imperial College London

ProfessorPaulFrench

Faculty of Natural SciencesDepartment of Physics

Professor of Physics and Vice Dean (Research) - FoNS
 
 
 
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Contact

 

+44 (0)20 7594 7706paul.french Website

 
 
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Assistant

 

Ms Judith Baylis +44 (0)20 7594 7713

 
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Location

 

609Blackett LaboratorySouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rutter:2016:10.1007/s00125-016-4025-1,
author = {Rutter, GA and Semplici, F and Mondragon, A and Macintyre, B and Madeyski-Bengston, K and Persson-Kry, A and Ramne, A and Marley, A and McGinty, J and French, P and Soedling, H and Yokosuka, R and Gaiten, J and Lang, J and Migrenne-Li, S and Philippe, E and Herrera, PL and Magnan, C and da, Silva Xavier G},
doi = {10.1007/s00125-016-4025-1},
journal = {Diabetologia},
pages = {1938--1947},
title = {Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production},
url = {http://dx.doi.org/10.1007/s00125-016-4025-1},
volume = {59},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Background and Aims. Per-Arnt-Sim domain containing kinase (PASK) is a nutrient regulated protein kinase previously implicated in the control of insulin gene expression and glucagon secretion. Here, we explore the roles of the kinase in the control of islet hormone release by generating mice deleted selectively for the Pask gene in pancreatic beta or alpha cells. Methods. Floxed alleles of Pask were produced by homologous recombination and animals bred with mice bearing beta (Ins1Cre, PaskBKO), or alpha (PPG-Cre; PaskAKO) cell selective Cre recombinase alleles. Glucose homeostasis and hormone secretion in vivo and in vitro, gene expression, and islet cell mass, were measured using standard techniques.Results. Ins1Cre-based recombination led to efficient beta cell targeted deletion of Pask. Beta cell mass was reduced by 36.5% (p<0.05) compared to controls in PaskBKO mice, as well as in global null Pask mice (38%, p<0.05). PaskBKO mice displayed normal body weight and fasting glycemia, but slightly impaired glucose tolerance, and beta cell proliferation, after maintenance on a high fat diet. Whilst glucose tolerance was unaffected in PaskAKO mice, glucose infusion rates were increased, and glucagon secretion tended to be lower, during hypoglycemic clamps. Though alpha cell mass was increased (21.9%, p<0.05), glucagon release at low glucose was impaired (p<0.05) in PaskAKO islets. Conclusions. The present findings demonstrate cell autonomous roles for PASK in the control of pancreatic endocrine hormone secretion. Differencesbetween the glycemic phenotype of global versus cell type specific null mice suggest important roles for tissue interactions in the control of glycemia by the kinase.
AU - Rutter,GA
AU - Semplici,F
AU - Mondragon,A
AU - Macintyre,B
AU - Madeyski-Bengston,K
AU - Persson-Kry,A
AU - Ramne,A
AU - Marley,A
AU - McGinty,J
AU - French,P
AU - Soedling,H
AU - Yokosuka,R
AU - Gaiten,J
AU - Lang,J
AU - Migrenne-Li,S
AU - Philippe,E
AU - Herrera,PL
AU - Magnan,C
AU - da,Silva Xavier G
DO - 10.1007/s00125-016-4025-1
EP - 1947
PY - 2016///
SN - 1432-0428
SP - 1938
TI - Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production
T2 - Diabetologia
UR - http://dx.doi.org/10.1007/s00125-016-4025-1
UR - http://hdl.handle.net/10044/1/33595
VL - 59
ER -