THE EFFECTS OF HYPERINSULINEMIA AND HYPERGLYCEMIA ON GLUT4 AND HEXOKINASE-II MESSENGER-RNA AND PROTEIN IN RAT SKELETAL-MUSCLE AND ADIPOSE-TISSUE

The GLUT4 glucose transporter and type II hexokinase are predominately expressed in skeletal muscle and adipose tissue. The effects of insul in and glucose on the expression of GLUT4 and HKII were studied in viv o by using the euglycemic-hyperinsulinemic and hyperglycemic-hyperinsu linemic clamp methods. The clamps were maintained in conscious rats fo r 6 or 24 h after a 1-day starvation period. Adipose tissue GLUT4 mRNA was increased 4-fold after 6 h and 23-fold after 24 h of hyperinsulin emia; HKII mRNA was increased by four- and eightfold after 6 and 24 h, respectively. In contrast, GLUT4 mRNA was not significantly changed i n skeletal muscle by either the euglycemic- or hyperglycemic-hyperinsu linemic clamps. Each of these treatments resulted in a fourfold induct ion of HKII mRNA. No changes of GLUT4 protein and hexokinase activity were detected after 6 h of hyperinsulinemia in either skeletal muscle or adipose tissue. After 24 h of hyperinsulinemia, adipose tissue GLUT 4 protein had doubled, whereas skeletal muscle GLUT4 was unchanged. In contrast, hexokinase activity increased by two- to eightfold in skele tal muscle and adipose tissue. Hyperinsulinemia alone was sufficient t o mediate the effects observed, because no additional effects were see n when hyperglycemia accompanied hyperinsulinemia. These results revea l the lack of coordinate regulation of GLUT4 and HKII in adipose tissu e and skeletal muscle. Whereas hyperinsulinemia increases both GLUT4 a nd HKII mRNA and protein levels in adipose tissue, this treatment incr eases HKII mRNA and protein in skeletal muscle, but has no effect on G LUT4 in this tissue.