Chronic stimulation of glucose transporter gene expression in L6 myocytes mediated via the insulin-like growth factor-1 receptor.
We have used differentiated L6 myocytes to investigate the regulation of glucose transporter gene expression by insulin and insulin-like growth factor-1 (IGF-1). Chronic exposure to insulin (1 microM) or IGF-1 (10 nm) resulted in a 2- to 5-fold stimulation of 3H-2-deoxy-D-glucose uptake and a corresponding increase in the expression of rat brain/HepG2-type glucose transporter mRNA (GTmRNA) and immunoreactive transporter protein. The dose responses to both insulin and IGF-1 for stimulation of glucose uptake were paralleled by the expression of GTmRNA. Glucose uptake and GTmRNA levels were half maximally stimulated by 350 and 100 nM insulin, respectively, or by 2 nM IGF-1. Comparison of receptor occupancy with stimulation of glucose uptake and GTmRNA expression suggests that insulin exerts its effects through the IGF-1 receptor. Fibroblast growth factor, epidermal growth factor, platelet-derived growth factor, and phorbol ester had little or no effect on GTmRNA expression. These results demonstrate that the IGF-1 receptor mediates chronic regulation of transporter mRNA expression and protein synthesis and activity in cultured rat muscle cells.
Maher
F
F
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Clark
S
S
Harrison
L C
LC
D000818:Animals; D002478:Cells, Cultured; D015342:DNA Probes; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D009132:Muscles / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000494:pharmacology*; D017451:Receptors, Somatomedin
D015342:DNA Probes; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D003847:Deoxyglucose