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Okamoto, Maristela Mitiko, Doris Hissako Sumida, Carla Roberta Oliveira Carvalho, Alessandra Martins Vargas, Joel Claudio Heimann, Beatriz D'Agord Schaan, and Ubiratan Fabres Machado. Changes in dietary sodium consumption modulate GLUT4 gene expression and early steps of insulin signaling. Am J Physiol Regul Integr Comp Physiol 286: R779-R785, 2004. First published December 11, 2003; 10.1152/ajpregu.00396.2003.--Previous studies have shown that chronic salt overload increases insulin sensitivity, while chronic salt restriction decreases it. In the present study we investigated the influence of dietary sodium on 1) GLUT4 gene expression, by Northern and Western blotting analysis; 2) in vivo GLUT4 protein translocation, by measuring the GLUT4 protein in plasma membrane and microsome, before and after insulin injection; and 3) insulin signaling, by analyzing basal and insulin-stimulated tyrosine phosphorylation of insulin receptor (IR)-[beta], insulin receptor substrate (IRS)-1, and IRS-2. Wistar rats were fed normal-sodium (NS-0.5%), low-sodium (LS-0.06%), or high-sodium diets (HS-3.12%) for 9 wk and were killed under pentobarbital anesthesia. Compared with NS rats, HS rats increased (P < 0.05) the GLUT4 protein in adipose tissue and skeletal muscle, whereas GLUT4 mRNA was increased only in adipose tissue. GLUT4 expression was unchanged in LS rats compared with NS rats. The GLUT4 translocation in HS rats was higher (P < 0.05) both in basal and insulin-stimulated conditions. On the other hand. LS rats did not increase the GLUT4 translocation after insulin stimulus. Compared with NS rats, LS rats showed reduced (P < 0.01) basal and insulin-stimulated tyrosine phosphorylatinn of IRS-1 in skeletal muscle and IRS-2 in liver, whereas HS rats showed enhanced basal tyrosine phosphorylation of IRS-1 in skeletal muscle (P < 0.05) and of IRS-2 in liver. In summary, increased insulin sensitivity in HS rats is related to increased GLUT4 gene expression, enhanced insulin signaling, and GLUT4 translocation, whereas decreased insulin sensitivity of LS rats does not involve changes in GLUT4 gene expression but is related to impaired insulin signaling. low-sodium diet; high-sodium diet; insulin resistance; GLUT4 gene expression; insulin signaling