Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice

The GLUT4 facilitative glucose transporter mediates insulin-dependent glucose uptake. We tested the hypothesis that moderate overexpression of human GLUT4 in mice, under the regulation of the human GLUT4 promoter, can prevent the hyperinsulinemia that results from obesity. Transgenic mice engineered...

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Main Authors:	Atkinson, Brittanie J., Griesel, Beth A., King, Caleb D., Josey, Miranda A., Olson, Ann Louise
Format:	Online
Language:	English
Published:	American Diabetes Association 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712063/

id	pubmed-3712063
recordtype	oai_dc
spelling	pubmed-37120632014-07-01 Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice Atkinson, Brittanie J. Griesel, Beth A. King, Caleb D. Josey, Miranda A. Olson, Ann Louise Original Research The GLUT4 facilitative glucose transporter mediates insulin-dependent glucose uptake. We tested the hypothesis that moderate overexpression of human GLUT4 in mice, under the regulation of the human GLUT4 promoter, can prevent the hyperinsulinemia that results from obesity. Transgenic mice engineered to express the human GLUT4 gene and promoter (hGLUT4 TG) and their nontransgenic counterparts (NT) were fed either a control diet (CD) or a high-fat diet (HFD) for up to 10 weeks. Homeostasis model assessment of insulin resistance scores revealed that hGLUT4 TG mice fed an HFD remained highly insulin sensitive. The presence of the GLUT4 transgene did not completely prevent the metabolic adaptations to HFD. For example, HFD resulted in loss of dynamic regulation of the expression of several metabolic genes in the livers of fasted and refed NT and hGLUT4 TG mice. The hGLUT4 TG mice fed a CD showed no feeding-dependent regulation of SREBP-1c and fatty acid synthase (FAS) mRNA expression in the transition from the fasted to the fed state. Similarly, HFD altered the response of SREBP-1c and FAS mRNA expression to feeding in both strains. These changes in hepatic gene expression were accompanied by increased nuclear phospho-CREB in refed mice. Taken together, a moderate increase in expression of GLUT4 is a good target for treatment of insulin resistance. American Diabetes Association 2013-07 2013-06-14 /pmc/articles/PMC3712063/ /pubmed/23474483 http://dx.doi.org/10.2337/db12-1146 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Atkinson, Brittanie J. Griesel, Beth A. King, Caleb D. Josey, Miranda A. Olson, Ann Louise
spellingShingle	Atkinson, Brittanie J. Griesel, Beth A. King, Caleb D. Josey, Miranda A. Olson, Ann Louise Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice
author_facet	Atkinson, Brittanie J. Griesel, Beth A. King, Caleb D. Josey, Miranda A. Olson, Ann Louise
author_sort	Atkinson, Brittanie J.
title	Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice
title_short	Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice
title_full	Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice
title_fullStr	Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice
title_full_unstemmed	Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice
title_sort	moderate glut4 overexpression improves insulin sensitivity and fasting triglyceridemia in high-fat diet–fed transgenic mice
description	The GLUT4 facilitative glucose transporter mediates insulin-dependent glucose uptake. We tested the hypothesis that moderate overexpression of human GLUT4 in mice, under the regulation of the human GLUT4 promoter, can prevent the hyperinsulinemia that results from obesity. Transgenic mice engineered to express the human GLUT4 gene and promoter (hGLUT4 TG) and their nontransgenic counterparts (NT) were fed either a control diet (CD) or a high-fat diet (HFD) for up to 10 weeks. Homeostasis model assessment of insulin resistance scores revealed that hGLUT4 TG mice fed an HFD remained highly insulin sensitive. The presence of the GLUT4 transgene did not completely prevent the metabolic adaptations to HFD. For example, HFD resulted in loss of dynamic regulation of the expression of several metabolic genes in the livers of fasted and refed NT and hGLUT4 TG mice. The hGLUT4 TG mice fed a CD showed no feeding-dependent regulation of SREBP-1c and fatty acid synthase (FAS) mRNA expression in the transition from the fasted to the fed state. Similarly, HFD altered the response of SREBP-1c and FAS mRNA expression to feeding in both strains. These changes in hepatic gene expression were accompanied by increased nuclear phospho-CREB in refed mice. Taken together, a moderate increase in expression of GLUT4 is a good target for treatment of insulin resistance.
publisher	American Diabetes Association
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712063/
_version_	1611994984892858368

Moderate GLUT4 Overexpression Improves Insulin Sensitivity and Fasting Triglyceridemia in High-Fat Diet–Fed Transgenic Mice

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