Time-dependent regulation of rat adipose tissue glucose transporter (GLUT4) mRNA and protein by insulin in streptozocin-diabetic and normal rats.
Streptozocin (STZ) administration (125 mg/kg) to normal rats resulted in a rapid (24-hour) decrease in circulating insulin levels, marked hyperglycemia, and weight loss. Adipose tissue glucose transporter 4 (GLUT4) mRNA levels decreased approximately eightfold, whereas GLUT4 protein levels were unchanged. However, GLUT4 protein levels decreased approximately 30% by 48 hours and fivefold by 72 hours of insulin deficiency. Although GLUT4 mRNA levels were rapidly restored by insulin therapy (twofold above control levels within 12 hours), GLUT4 protein levels increased only gradually, reaching peak values of 1.5-fold control levels following 7 to 10 days of insulin treatment. Insulin treatment in normal rats increased adipose GLUT4 mRNA levels nearly 100% by 24 hours, while GLUT4 protein levels increased in a more gradual fashion. The delay in GLUT4 protein induction relative to its mRNA was shorter in normal rats treated with insulin than in insulin-treated diabetic rats. These data demonstrate that insulin-induced changes in adipose GLUT4 protein are considerably delayed relative to its mRNA, and that the diabetic state enhances this difference. The known in vivo time-dependent effects of insulin treatment on adipocyte glucose transport activity can be at least partly explained by altered specific expression of GLUT4 protein.
Sivitz
W I
WI
Department of Internal Medicine, University of Iowa, Iowa City.
DeSautel
S L
SL
Lee
E C
EC
Pessin
J E
JE
D000818:Animals; D003921:Diabetes Mellitus, Experimental; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D013311:Streptozocin