Improvement of insulin action in diabetic transgenic mice selectively overexpressing GLUT4 in skeletal muscle.
To investigate the role of glucose transporter expression in whole-body glucose homeostasis, we have created transgenic mice that have a 2.0- to 3.5-fold increase in GLUT4 glucose transporter level in skeletal muscle and heart. This increase is sufficient to significantly improve insulin action and to reduce basal blood glucose levels in transgenic streptozotocin-induced diabetic mice. These results provide the first evidence of a direct causality between skeletal muscle GLUT4 transporter level and overall insulin responsiveness.
Leturque
A
A
Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, Meudon-Bellevue, France.
Loizeau
M
M
Vaulont
S
S
Salminen
M
M
Girard
J
J
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D015153:Blotting, Western; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D003847:Deoxyglucose