EFFECTS AND BINDING OF INSULIN-LIKE GROWTH FACTOR-I IN THE ISOLATED SOLEUS MUSCLE OF LEAN AND OBESE MICE - COMPARISON WITH INSULIN

The effects and binding of insulin-like growth factor-I (IGF-I) in skeletal muscle were investigated in the isolated mouse soleus muscle from normal lean and goldthioglucose- obese mice. In muscles from lean mice, IGF-I stimulated 2-deoxyglucose uptake, glycolysis, and glycogen synthesis and activated glycogen synthase. The latter effect occurred in the absence of glucose in the incubation medium, as was also observed with insulin. The maximal effects of IGF-I and insulin on 2-deoxyglucose uptake were not additive. IGF-I was about 4–9% as potent as insulin (half-maximal effects occurred with 5-14 nM IGF-I) and nearly as effective as insulin. A specific binding of [125I]iodo-IGF-I was observed, which was not inhibited by unlabeled insulin or proinsulin. IGF-I was less than 1% (on a molar basis) as potent as insulin in competing with [125I]iodoinsulin binding. Unlike [125I]iodoinsulin binding, [125I]iodo-IGF-l binding was similar in muscles from lean and goldthioglucose-obese mice. As observed with insulin, however, the effects of IGF-I on 2- deoxyglucose uptake and glycogen synthase were markedly depressed in muscles from obese mice compared to lean controls. These findings indicate that, in skeletal muscle, IGF-I exerts insulin-like effects with an intermediate potency between that observed in fat cells and heart muscle. The data also suggest that, in skeletal muscle, IGF-I exerts insulin-like effects through its own specific receptors, whereas IGF-I and insulin appear to stimulate the same glucose transport system and activate glycogen synthase through a common pathway. © 1979 by The Endocrine Society.