PMID:12097321

Citation	Gray, S, Feinberg, MW, Hull, S, Kuo, CT, Watanabe, M, Sen-Banerjee, S, DePina, A, Haspel, R and Jain, MK (2002) The Krüppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J. Biol. Chem. 277:34322-8
Abstract	Resistance to the stimulatory effects of insulin on glucose utilization is a key feature of type 2 diabetes, obesity, and the metabolic syndrome. Recent studies suggest that insulin resistance is primarily caused by a defect in glucose transport. GLUT4 is the main insulin-responsive glucose transporter and is expressed predominantly in muscle and adipose tissues. Whereas GLUT4 has been shown to play a critical role in maintaining systemic glucose homeostasis, the mechanisms regulating its expression are incompletely understood. We have cloned the murine homologue of KLF15, a member of the Krüppel-like family of transcription factors. KLF15 is highly expressed in adipocytes and myocytes in vivo and is induced when 3T3-L1 preadipocytes are differentiated into adipocytes. Overexpression of KLF15 in adipose and muscle cell lines potently induces GLUT4 expression. This effect is specific to KLF15 as overexpression of two other Krüppel-like factors, KLF2/LKLF and KLF4/GKLF, did not induce GLUT4 expression. Both basal (3.3-fold, p < 0.001) and insulin-stimulated (2.4-fold, p < 0.00001) glucose uptake are increased in KLF15-overexpressing adipocytes. In co-transfection assays, KLF15 and MEF2A, a known activator of GLUT4, synergistically activates the GLUT4 promoter. Promoter deletion and mutational analyses provide evidence that this activity requires an intact KLF15-binding site proximal to the MEF2A site. Finally, co-immunoprecipitation assays show that KLF15 specifically interacts with MEF2A. These studies indicate that KLF15 is an important regulator of GLUT4 in both adipose and muscle tissues.
Links	PubMed Online version:10.1074/jbc.M201304200
Keywords	3T3 Cells; Adipose Tissue/metabolism; Amino Acid Sequence; Animals; CCAAT-Enhancer-Binding Protein-alpha/physiology; DNA/metabolism; DNA-Binding Proteins/analysis; DNA-Binding Proteins/physiology; Gene Expression Regulation; Glucose/metabolism; Glucose Transporter Type 4; Kruppel-Like Transcription Factors; Mice; Molecular Sequence Data; Monosaccharide Transport Proteins/genetics; Muscle Proteins; Muscle, Skeletal/metabolism; Myogenic Regulatory Factors; Promoter Regions, Genetic; Repressor Proteins; Transcription Factors/analysis; Transcription Factors/physiology; Transcriptional Activation
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