INVIVO REGULATION OF MESSENGER-RNA ENCODING INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND ITS RECEPTOR BY DIABETES, INSULIN AND IGF-I IN RAT MUSCLE

The effects of continuous or acute administration of insulin or insulin-like growth factor-I (IGF-I) on IGF-I mRNA and IGF-I receptor mRNA were studied in the skeletal muscle (gastrocnemius), heart muscle and vascular smooth muscle (aorta) of non-diabetic and diabetic rats using a solution hybridization assay. The levels of IGF-I mRNA in the different types of muscle markedly decreased by diabetes, whereas changes in IGF-I receptor mRNA were less consistent. Continuous infusion of diabetic rats with insulin (28 or 35 nmol/day) for 4 days normalized the altered levels of IGF-I mRNA and IGF-I receptor mRNA. Infusion of equimolar concentrations of IGF-I did not affect IGF-I mRNA, but decreased the level of IGF-I receptor mRNA in skeletal muscle. In acute experiments, rats were injected with equipotent blood glucose-lowering doses of insulin (14 nmol) or IGF-I (107 nmol). Insulin did not significantly affect levels of IGF-I mRNA, but decreased levels of IGF-I receptor mRNA in skeletal muscle and aorta. IGF-I increased levels of IGF-I mRNA in heart muscle, and markedly decreased levels of IGF-I receptor mRNA in skeletal muscle and heart muscle from non-diabetic and diabetic rats. In conclusion. exogenous IGF-I and insulin can increase IGF-I mRNA and decrease IGF-I receptor mRNA. indicating that both insulin and IGF-I can act as regulators of the IGF-I system in muscle in vivo.