title: Differential regulation of glucose transporter activity and expression in red and white skeletal muscle.
abstract: Insulin-stimulated glucose transport activity and GLUT4 glucose transporter protein expression in rat soleus, red-enriched, and white-enriched skeletal muscle were examined in streptozotocin (STZ)-induced insulin-deficient diabetes. Six days of STZ-diabetes resulted in a nearly complete inhibition of insulin-stimulated glucose transport activity in perfused soleus, red, and white muscle which recovered following insulin therapy. A specific decrease in the GLUT4 glucose transporter protein was observed in soleus (3-fold) and red (2-fold) muscle which also recovered to control values with insulin therapy. Similarly, cardiac muscle displayed a marked STZ-induced decrease in GLUT4 protein that was normalized by insulin therapy. White muscle displayed a small but statistically significant decrease in GLUT4 protein (23%), but this could not account for the marked inhibition of insulin-stimulated glucose transport activity observed in this tissue. In addition, GLUT4 mRNA was found to decrease in red muscle (2-fold) with no significant alteration in white muscle. The effect of STZ-induced diabetes was time-dependent with maximal inhibition of insulin-stimulated glucose transport activity at 24 h in both red and white skeletal muscle and half-maximal inhibition at approximately 8 h. In contrast, GLUT4 protein in red and white muscle remained unchanged until 4 and 7 days following STZ treatment, respectively. These data demonstrate that red skeletal muscle displays a more rapid hormonal/metabolic-dependent regulation of GLUT4 glucose transporter protein and mRNA expression than white skeletal muscle. In addition, the inhibition of insulin-stimulated glucose transport activity in both red and white muscle precedes the decrease in GLUT4 protein and mRNA levels. Thus, STZ treatment initially results in a rapid uncoupling of the insulin-mediated signaling of glucose transport activity which is independent of GLUT4 protein and mRNA levels.
authors.affiliation: Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City.
authors.forename: J M
authors.initials: JM
authors.lastname: Richardson
authors.forename: T W
authors.initials: TW
authors.lastname: Balon
authors.forename: J L
authors.initials: JL
authors.lastname: Treadway
authors.forename: J E
authors.initials: JE
authors.lastname: Pessin
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D013311:Streptozocin