Differential regulation of adipose tissue glucose transporters in genetic obesity (fatty rat). Selective increase in the adipose cell/muscle glucose transporter (GLUT 4) expression

Abstract

Adipocytes from young obese Zucker rats exhibit a hyperresponsive insulin-mediated glucose transport, together with a marked increase in cytochalasin B binding as compared with lean rat adipocytes. Here, we examined in these cells the expression of two isoforms of glucose transporter, the erythroid (GLUT 1) and the adipose cell/muscle (GLUT 4) types, in rats aged 16 or 30 d, i.e., before and after the emergence of hyperinsulinemia. GLUT 1 protein and mRNA levels were identical in the two genotypes at both ages. In contrast, the levels of GLUT 4 protein in obese rat adipocytes were 2.4- and 4.5-fold those of lean littermates at 16 and 30 d of age, respectively, in perfect agreement with the genotype effect on insulin-stimulated glucose transport activity. The levels of GLUT 4 mRNA per fat pad were increased 2.3- and 6.2-fold in obese vs. lean rats 16- and 30-d-old, indicating a pretranslational level of regulation. The obese phenotype was not associated with overexpression of GLUT 4 mRNA in gastrocnemius muscle. This work indicates that the fa gene exerts a differential control on the expression of GLUT 1 and GLUT 4 in adipose tissue and provides evidence that independent of hyperinsulinemia, genotype is a major regulatory factor of GLUT 4 expression in this tissue.