Divergence between GLUT4 mRNA and protein abundance in skeletal muscle of insulin resistant rats.
Hyperglycemia and skeletal muscle insulin resistance coexist in uncontrolled type 2 diabetes mellitus. Similar defects in insulin action were observed in glucose-infused, normal rats, a model of glucose toxicity. In these rats insulin-stimulated glucose uptake by skeletal muscle was decreased due to a post-receptor defect. We investigated whether the impaired glucose uptake resulted from a decrease in the abundance of the predominant muscle glucose transporter (GLUT4) mRNA and/or protein. GLUT4 protein abundance in the hyperglycemic rats was not different from the control group despite a 50% decrease in muscle glucose uptake. GLUT4 mRNA abundance was 2.5-fold greater in the hyperglycemic rats as compared to the control animals. We conclude that the coexistence of hyperglycemia and hyperinsulinemia results in (1) a defect in GLUT4 compartmentalization and/or functional activity and (2) a divergence between GLUT4 mRNA levels and translation.
Hager
S R
SR
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Pastorek
D
D
Jochen
A L
AL
Meier
D
D
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D009132:Muscles / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger