Comparative effects of IGF-I and insulin on the glucose transporter system in rat muscle.
The acute effect of insulin-like growth factor I (IGF-I) and insulin on glucose uptake and the glucose transport system in in vitro incubated rat soleus muscles was examined using 3-O-methylglucose and the ATB-[3H]BMPA exofacial photolabeling technique. IGF-I and insulin both stimulated 3-O-methylglucose uptake and GLUT-4 translocation in a dose-dependent manner with a maximal effect six- to sevenfold above basal. No additive effects of IGF-I and insulin on maximal 3-O-methylglucose uptake were found. On a molar basis, IGF-I was 13 times less potent than insulin. Receptor binding experiments showed that IGF-I exhibited a much lower affinity for the insulin receptor [half-maximal effective dose (ED50) = 28.5 nM] than that of insulin (ED50 = 0.20 nM). In contrast, IGF-I bound to the partially purified IGF-I receptor with an apparent affinity (ED50 = 3.7 nM) that was similar to the concentrations of IGF-I which caused half-maximal activation of 3-O-methylglucose uptake (ED50 = 2.4 nM) and GLUT-4 translocation (ED50 = 2.5 nM). Our findings suggest that IGF-I exerts its insulin-like effects on glucose uptake primarily through its own specific receptor and that the molecular events underlying IGF-I and insulin actions on glucose uptake in skeletal muscle are similar, namely caused by a translocation of the GLUT-4 transporter from an intracellular pool to the cell surface.
Lund
S
S
Department of Biochemistry, University of Bath, United Kingdom.
Flyvbjerg
A
A
Holman
G D
GD
Larsen
F S
FS
Pedersen
O
O
Schmitz
O
O
D019325:3-O-Methylglucose; D000345:Affinity Labels; D000818:Animals; D001386:Azides; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004187:Disaccharides; D006027:Glycosides; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D011437:Propylamines; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism
D000345:Affinity Labels; D001386:Azides; D004187:Disaccharides; D006027:Glycosides; D007328:Insulin; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D011437:Propylamines; C065412:2-N-(4-(1-azitrifluoroethyl)benzoyl)-1,3-bis-(mannos-4-yloxy)-2-propylamine; D019325:3-O-Methylglucose; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin