Insulin-like growth factor I (IGF-I) is a more potent regulator of gene expression than insulin in primary human myoblasts and myotubes.
Conventionally, insulin is believed to induce a metabolic response, and IGF-I a mitogenic/differentiation response in vivo. However, several studies indicate that the roles of insulin and IGF-I may not be that easy to separate. In this study, insulin and IGF-I specificity in terms of gene regulation was investigated in primary human skeletal muscle cells before and after differentiation. Cell cultures were treated with 100 nM insulin, IGF-I or nothing for 4h, and gene expression was subsequently determined using the Affymetrix microarray platform. Insulin and IGF-I receptor levels were determined by qRT-PCR and by radioligand binding assays. In primary myoblasts, insulin did not have any significant effect on gene expression, whereas IGF-I regulated 229 genes. In primary myotubes, insulin regulated 105 genes, whereas IGF-I regulated 697 genes. Additionally, 99 genes were found to be differentially regulated by insulin and IGF-I in a direct comparison. The majority of these genes were specifically regulated by IGF-I, 16 genes were regulated by both ligands, and no genes were regulated by only insulin. The microarray results correlated with low levels of insulin receptors compared to IGF-I receptors as determined by radioligand binding assays. In the myotubes, we did not identify any ligand specificity in terms of functional categories. The major difference between the two ligands was their respective potencies in gene regulation, which was higher for IGF-I than for insulin. This was true for genes involved in both mitogenic and metabolic regulations. The data suggest that IGF-I is a more important metabolic regulator in skeletal muscle than previously estimated.
Palsgaard
Jane
J
Receptor Systems Biology Laboratory, Hagedorn Research Institute, Niels Steensens vej 6, 2820 Gentofte, Denmark. JPAG@novonordisk.com
Brown
Audrey E
AE
Jensen
Maja
M
Borup
Rehannah
R
Walker
Mark
M
De Meyts
Pierre
P
D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
D007328:Insulin; D007334:Insulin-Like Growth Factor I