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PERSPECTIVES

Transcriptional regulation of the insulin-responsive glucose transporter GLUT4 gene: from physiology to pathology

Institute of Endocrinology, Diabetes and Metabolism, Rambam Medical Center and R. B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Submitted 20 March 2008 ; accepted in final form 16 May 2008

ABSTRACT

The insulin-responsive glucose transporter 4 (GLUT4) plays a key role in glucose uptake and metabolism in insulin target tissues. Being a rate-limiting step in glucose metabolism, the expression and function of the GLUT4 isoform has been extensively studied and found to be tightly regulated at both mRNA and protein levels. Adaptation to states of enhanced metabolic demand is associated with increased glucose metabolism and GLUT4 gene expression, whereas states of insulin resistance such as type 2 diabetes mellitus (DM2), obesity, and aging are associated with impaired regulation of GLUT4 gene expression and function. The present review focuses on the interplay among hormonal, nutritional, and transcription factors in the regulation of GLUT4 transcription in health and sickness.

adipose; diabetes; gene expression; muscle; obesity; peroxisome proliferator-activated receptor-; forkhead box O1