The regulation by insulin of glucose transporter gene expression in 3T3 adipocytes.
The effect of insulin on the expression of the gene encoding the rat brain glucose transporter (GT) was studied in 3T3 F442A murine adipocytes. Differentiation from fibroblasts into adipocytes did not alter the basal expression of this gene, but did confer on the cells the ability to accumulate GT mRNA in response to insulin. Concentrations of the hormone less than 40 nM were capable of stimulating about a 5-fold increase in GT mRNA in adipocytes, whereas insulin was without effect in fibroblasts. The stimulation in adipocytes by insulin was maximal 4 h after the addition of the hormone and was preceded by a 4-6-fold augmentation in the transcription of the GT gene. In NIH/3T3 HIR3.5 cells, which express 3 X 10(6) insulin receptors per cell due to the introduction of the receptor cDNA by DNA-mediated gene transfer (Whittaker, J., Okamoto, A., Thyss, R., Bell, G.I., Steiner, D.F., and Hofmann, C. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5237-5241), insulin increased GT mRNA levels at the same concentrations and to the same extent as in adipocytes. The augmentation in GT gene expression in HIR3.5 cells occurred 3-4 h of addition of insulin correlated with a 3-4-fold increase in glucose transport in these cells. These data demonstrate that: 1) the differentiation from fibroblasts to adipocytes is accompanied by the acquisition of an insulin-stimulated mechanism for the regulation of GT gene expression. 2) In fibroblasts, the limiting factor in the pathway regulating GT mRNA levels by insulin is the low number of receptors, since their expression by gene transfer in the absence of differentiation is sufficient to confer sensitivity to insulin.
Garcia de Herreros
A
A
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
Birnbaum
M J
MJ
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D003847:Deoxyglucose; D013755:Tetradecanoylphorbol Acetate