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Regulation of GLUT4 gene expression by SREBP-1c in adipocytes

 Seung-Soon IM  ;  Sool-Ki KWON  ;  Seung-Youn KANG  ;  Tae-Hyun KIM  ;  Ha-Il KIM  ;  Man-Wook HUR  ;  Kyung-Sup KIM  ;  Yong-Ho AHN 
 BIOCHEMICAL JOURNAL, Vol.399(1) : 131-139, 2006 
Journal Title
Issue Date
3T3-L1 Cells ; Adipocytes/cytology ; Adipocytes/metabolism* ; Animals ; Cell Differentiation ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/metabolism ; Eating ; Fasting ; Gene Expression Regulation*/drug effects ; Glucose Transporter Type 4/genetics* ; Humans ; Insulin/pharmacology ; Male ; Mice ; Promoter Regions, Genetic ; Rats ; Response Elements/genetics ; Sp1 Transcription Factor/metabolism ; Sterol Regulatory Element Binding Protein 1/genetics ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Up-Regulation/drug effects
adipocytes ; insulin ; sterol-response element ; sterol-regulatory-element-binding protein-1c (SREBP-1c) ; type 4 glucose transporter isoform (GLUT4)
Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes is subject to hormonal or metabolic control. In the present study, we have characterized an adipose tissue transcription factor that is influenced by fasting/refeeding regimens and insulin. Northern blotting showed that refeeding increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory-element-binding protein)-1c in adipose tissue were also increased by refeeding. In streptozotocin-induced diabetic rats, insulin treatment increased the mRNA levels of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays and electrophoretic mobility-shift assay studies indicated that the putative sterol response element is located in the region between bases -109 and -100 of the human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4, suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to the putative sterol-response element in the GLUT4. Furthermore, treating streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In addition, we have identified an Sp1 binding site adjacent to the functional sterol-response element in the GLUT4 promoter. The Sp1 site appears to play an additive role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest that upregulation of GLUT4 gene transcription might be directly mediated by SREBP-1c in adipose tissue.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
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