Effects of altered glucose homeostasis on glucose transporter expression in skeletal muscle of the rat.
Previous studies have suggested that alteration in the expression of the insulin-regulatable glucose transporter of muscle (GLUT-4 protein) may be an important determinant of insulin action. In the present studies, we have examined GLUT-4 mRNA and protein concentrations in muscle after variations in the metabolic status of the intact animal (i.e., 7 d streptozotocin-induced diabetes, 7 d insulin-induced hypoglycemia, and 3 d fasting). These changes in glucose homeostasis were associated with the following changes in GLUT-4 gene products: a decrease of approximately 30% in both mRNA and protein with diabetes; a 50% increase in mRNA and a 2.4-fold increase in protein with insulin injection; and normal mRNA in spite of a 2.7-fold increase in protein with fasting. Fasted diabetics exhibited an increase of 50% in GLUT-4 mRNA and a 2.4-fold increase in protein relative to fed diabetics. In diabetic and insulin-injected groups, the changes in GLUT-4 protein were similar to changes in mRNA, but in fasting, GLUT-4 protein increased without a concomitant change in mRNA. Overall there was no correlation between muscle concentrations of GLUT-4 protein and mRNA. Muscle GLUT-4 protein concentration tended to correlate with plasma glucose (r = -0.57, P less than 0.001), but not with plasma insulin. These results indicate that (a) chronic changes in glucose homeostasis are associated with changes in expression of GLUT-4 protein in muscle; (b) GLUT-4 protein increased in fasted soleus muscle without change in mRNA, thereby differing from fasted adipocytes in which both GLUT-4 products diminish; and (c) no simple relationship exists between total muscle GLUT-4 protein content and whole-body insulin sensitivity.
Bourey
R E
RE
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Koranyi
L
L
James
D E
DE
Mueckler
M
M
Permutt
M A
MA
D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005215:Fasting; D015870:Gene Expression; D006706:Homeostasis; D007003:Hypoglycemia / Q000503:physiopathology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger