Imperial College London
Alternate

ProfessorGuyRutter

Faculty of Medicine, Department of Medicine

Visiting Professor
 
 
 
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Contact

 

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

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Amouyal:2020:10.1016/j.ebiom.2020.102895,
author = {Amouyal, C and Castel, J and Guay, C and Lacombe, A and Denom, J and Migrenne-Li, S and Rouault, C and Marquet, F and Georgiadou, E and Stylianides, T and Luquet, S and Le, Stunff H and Scharfmann, R and Clément, K and Rutter, GA and Taboureau, O and Magnan, C and Regazzi, R and Andreelli, F},
doi = {10.1016/j.ebiom.2020.102895},
journal = {EBioMedicine},
title = {A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice},
url = {http://dx.doi.org/10.1016/j.ebiom.2020.102895},
volume = {58},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our aim was to identify pathways, evident in the islet transcriptome, that characterize the adaptive response to bariatric surgery independently of body weight changes. METHODS: We performed entero-gastro-anastomosis (EGA) with pyloric ligature in leptin-deficient ob/ob mice as a surrogate of Roux-en-Y gastric bypass (RYGB) in humans. Multiple approaches such as determination of glucose tolerance, GLP-1 and insulin secretion, whole body insulin sensitivity, ex vivo glucose-stimulated insulin secretion (GSIS) and functional multicellular Ca2+-imaging, profiling of mRNA and of miRNA expression were utilized to identify significant biological processes involved in pancreatic islet recovery. FINDINGS: EGA resolved diabetes, increased pancreatic insulin content and GSIS despite a persistent increase in fat mass, systemic and intra-islet inflammation, and lipotoxicity. Surgery differentially regulated 193 genes in the islet, most of which were involved in the regulation of glucose metabolism, insulin secretion, calcium signaling or beta cell viability, and these were normalized alongside changes in glucose metabolism, intracellular Ca2+ dynamics and the threshold for GSIS. Furthermore, 27 islet miRNAs were differentially regulated, four of them hubs in a miRNA-gene interaction network and four others part of a blood signature of diabetes resolution in ob/ob mice and in humans. INTERPRETATION: Taken together, our data highlight novel miRNA-gene interactions in the pancreatic islet during the resolution of diabetes after bariatric surgery that form part of a blood signature of diabetes reversal. FUNDING: European Union's Horizon 2020 research and innovation programme via the Innovat
AU  - Amouyal,C
AU  - Castel,J
AU  - Guay,C
AU  - Lacombe,A
AU  - Denom,J
AU  - Migrenne-Li,S
AU  - Rouault,C
AU  - Marquet,F
AU  - Georgiadou,E
AU  - Stylianides,T
AU  - Luquet,S
AU  - Le,Stunff H
AU  - Scharfmann,R
AU  - Clément,K
AU  - Rutter,GA
AU  - Taboureau,O
AU  - Magnan,C
AU  - Regazzi,R
AU  - Andreelli,F
DO  - 10.1016/j.ebiom.2020.102895
PY  - 2020///
SN  - 2352-3964
TI  - A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2020.102895
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32739864
UR  - http://hdl.handle.net/10044/1/81566
VL  - 58
ER  -
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