In-vivo 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-1 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.
Bornfeldt
K E
KE
Department of Pharmacology, Faculty of Health Sciences, Linköping University, Sweden.
Skottner
A
A
Arnqvist
H J
HJ
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D007328:Insulin / Q000235:genetics* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics*
D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1