Changes in dietary sodium consumption modulate GLUT4 gene expression and early steps of insulin signaling.
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 No the n 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 we e fed no mal-sodium (NS-0.5%), low-sodium (LS-0.06%), o high-sodium diets (HS-3.12%) fo 9 wk and were killed under pentobarbital anesthesia. Compared with NS ats, HS ats inc eased (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 ats compared with NS ats. The GLUT4 translocation in HS ats was higher (P < 0.05) both in basal and insulin-stimulated conditions. On the other hand, LS ats did not increase the GLUT4 translocation after insulin stimulus. Compared with NS ats, LS ats showed reduced (P < 0.01) basal and insulin-stimulated tyrosine phosphorylation of IRS-1 in skeletal muscle and IRS-2 in live, whereas HS ats showed enhanced basal tyrosine phosphorylation of IRS-1 in skeletal muscle (P < 0.05) and of IRS-2 in live. In summary, increased insulin sensitivity in HS ats is elated to increased GLUT4 gene expression, enhanced insulin signaling, and GLUT4 translocation, whereas decreased insulin sensitivity of LS ats does not involve changes in GLUT4 gene expression but is elated to impaired insulin signaling.
Okamoto
Maristela Mitiko
MM
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 05508-900, São Paulo, Brazil.
Sumida
Dóris Hissako
DH
Carvalho
Carla Roberta Oliveira
CR
Vargas
Alessandra Martins
AM
Heimann
Joel Cláudio
JC
Schaan
Beatriz D'Agord
BD
Machado
Ubiratan Fabres
UF
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D005786:Gene Expression Regulation / Q000187:drug effects*; D051275:Glucose Transporter Type 4; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012982:Sodium, Dietary / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D012982:Sodium, Dietary; D014443:Tyrosine; D011972:Receptor, Insulin