Hormonal/metabolic regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice

Ann Louise Olson; Min-Ling Liu; W Scott Moye-Rowley; John B Buse; Graeme I Bell; Jeffrey E Pessin

doi:10.1016/S0021-9258(18)98422-X

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Hormonal/metabolic regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice

Journal article

Open access

Peer reviewed

Hormonal/metabolic regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice

Ann Louise Olson, Min-Ling Liu, W Scott Moye-Rowley, John B Buse, Graeme I Bell and Jeffrey E Pessin

The Journal of biological chemistry, Vol.268(13), pp.9839-9846

1993

DOI: 10.1016/S0021-9258(18)98422-X

PMID: 8486663

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Abstract

To examine the hormonal/metabolic as well as tissue-specific expression of the GLUT4/muscle-fat facilitative glucose transporter gene, we have generated several transgenic mouse lines expressing a human GLUT4 mini-gene which extends 5.3 kilobases (kb) upstream of transcription start and terminates within exon 10. This construct (hGLUT4-11.5) was expressed in a tissue- specific pattern identical to the endogenous mouse GLUT4 gene. The transcription initiation sites of the transgenic construct were similar to the GLUT4 gene expressed in human tissues. To investigate the hormonal/metabolic-dependent regulation of GLUT4, the transgenic animals were made insulin-deficient by streptozotocin (STZ) treatment. In these animals, STZ-induced diabetes resulted in a parallel decrease in endogenous mouse GLUT4 mRNA and the transgenic human GLUT4 mRNA in white adipose tissue, brown adipose tissue, and cardiac muscle. Similarly, insulin treatment of the STZ- diabetic animals restored both the endogenous mouse and transgenic human GLUT4 mRNA levels. To further define cis-regulatory regions responsible for this hormonal/metabolic regulation, the same analysis was performed on transgenic animals which carry 2.4 kb of the human GLUT4 5'-flanking region fused to a CAT reporter gene (hGLUT4[2.4]-CAT). This reporter construct responded similarly to the human GLUT4 mini-gene demonstrating that the element(s) controlling hormonal/metabolic regulation and tissue specificity all reside exclusively within 2.4 kb of the transcriptional initiation site.

Molecular Genetics

Biological and medical sciences

Fundamental and applied biological sciences. Psychology

Molecular and cellular biology

Transcription. Transcription factor. Splicing. Rna processing

Details

Title: Subtitle: Hormonal/metabolic regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice
Creators: Ann Louise Olson - University of Iowa
Min-Ling Liu - University of Iowa
W Scott Moye-Rowley - University of Iowa
John B Buse - University of Iowa
Graeme I Bell - University of Iowa
Jeffrey E Pessin - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.268(13), pp.9839-9846
DOI: 10.1016/S0021-9258(18)98422-X
PMID: 8486663
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology
Language: English
Date published: 1993
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984297610702771

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