Insulin-like growth factor 1 inhibits glucocorticoid-induced glutamine synthetase activity in cultured L6 rat skeletal muscle cells.
We previously demonstrated the preventive effect of insulin-like growth factor 1 (IGF-1) on steroid myopathy in rats. However, the mechanism by which IGF-1 inhibits steroid myopathy remains unclear. Recent studies have revealed that glutamine synthetase (GS) is induced by glucocorticoid and may be related to the development of steroid myopathy. In this study, we examined whether IGF-1 affected steroid-induced enhancement of GS activity in L6 rat skeletal muscle cells. Dexamethasone (10(-6) M) significantly increased GS activity in L6 cells (P < 0.01). IGF-1 dose-dependently inhibited dexamethasone-induced GS activity. Addition of IGF-1 (750 ng/ml) decreased GS activity to approximately 50% of that with dexamethasone alone (P < 0.01). These results suggest that a decrease in GS activity may be involved in the preventive effect of IGF-1 on steroid myopathy.
Kimura
K
K
Third Division, Department of Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan.
Kanda
F
F
Okuda
S
S
Chihara
K
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects* / Q000201:enzymology*; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D005974:Glutamate-Ammonia Ligase / Q000187:drug effects* / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D051381:Rats
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D005973:Glutamine; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D005974:Glutamate-Ammonia Ligase