Imperial College London
Alternate

Dr Aida Martinez-Sanchez

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3366a.martinez-sanchez Website

 
 
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Location

 

326ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Nguyen-Tu:2020:10.1101/2020.05.18.102384,
author = {Nguyen-Tu, M-S and Martinez-Sanchez, A and Leclerc, I and Rutter, GA and da, Silva Xavier G},
doi = {10.1101/2020.05.18.102384},
title = {Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice},
url = {http://dx.doi.org/10.1101/2020.05.18.102384},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>Transcription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/beta-catenin signalling pathway and its expression is critical for adipocyte development. The precise role of TCF7L2 in glucose and lipid metabolism in adult adipocytes remains to be defined. Here, we aim to investigate how changes in TCF7L2 expression in mature adipocytes affect glucose homeostasis. <jats:italic>Tcf7l2</jats:italic> was selectively ablated from mature adipocytes in C57BL/6J mice using an adiponectin promoter-driven <jats:italic>Cre</jats:italic> recombinase to recombine alleles floxed at exon 1 of the <jats:italic>Tcf7l2</jats:italic> gene. Mice lacking <jats:italic>Tcf7l2</jats:italic> in mature adipocytes displayed normal body weight. Male mice exhibited normal glucose homeostasis at eight weeks of age. Male heterozygote knockout mice (aTCF7L2het) exhibited impaired glucose tolerance (AUC increased 1.14 ± 0.04 -fold, p=0.03), as assessed by intraperitoneal glucose tolerance test, and changes in fat mass at 16 weeks (increased by 1.4 ± 0.09-fold, p=0.007). Homozygote knockout mice exhibited impaired oral glucose tolerance at 16 weeks of age (AUC increased 2.15 ± 0.15-fold, p=0.0001). Islets of Langerhans exhibited impaired glucose-stimulated insulin secretion <jats:italic>in vitro</jats:italic> (decreased 0.54 ± 0.13-fold aTCF7L2KO vs control, p=0.02), but no changes in <jats:italic>in vivo</jats:italic> glucose-stimulated insulin secretion. Female mice in which one or two alleles of the <jats:italic>Tcf7l2</jats:italic> gene was knocked out in adipocytes displayed no changes in glucose tolerance, insulin sensitivity or insulin secretion. Plasma levels of glucagon-like peptide-1 and gastric inhibitory polypeptide were lowered in knockout mice (decreased 0.57 ± 0.03-fold and 0.41 ± 0.12-fold
AU  - Nguyen-Tu,M-S
AU  - Martinez-Sanchez,A
AU  - Leclerc,I
AU  - Rutter,GA
AU  - da,Silva Xavier G
DO  - 10.1101/2020.05.18.102384
PY  - 2020///
TI  - Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice
UR  - http://dx.doi.org/10.1101/2020.05.18.102384
ER  -
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