INSULIN-LIKE GROWTH FACTOR-I AND INSULIN-RESISTANCE IN SKELETAL-MUSCLES OF ADULT AND OLD RATS

A study was designed to compare the effects, in vitro, of insulin-like growth factor-1 (IGF-1) and insulin on rat epitrochlearis muscle meta bolism during aging (1, 6-8, or 18-20 months). Our results showed that in young epitrochlearis, IGF-1 was equipotent to insulin in stimulati ng 2-deoxy-glucose and aminoisobutyric acid transport but more potent in increasing tyrosine incorporation into protein. Both insulin and IG F-1 action on glucose transport was decreased in adult compared with y oung muscle. Whereas an insulin resistance of amino acid transport and protein synthesis was also recorded in adult rat muscle, the stimulat ory effect of IGF-1 on these processes was abolished. Thus the degree of resistance observed varied both with the agonist and with the subse quent metabolic process observed. Whereas modifications of IGF-1 actio n in mature animals may be correlated in part to the dramatic decrease of IGF-1 receptors (80%), no similar observations were recorded for t he insulin receptor. Since muscle IGF-1 receptor gene expression did n ot decrease in parallel with receptor number, an alteration in IGF-1 r eceptor messenger RNA (mRNA) translation or receptor degradation may b e hypothetized. We concluded that: 1) In contrast to glucose transport , intracellular IGF-1 and insulin postreceptor pathways leading to ami no acid uptake and protein metabolism differ. 2) Modification in postb inding events might be involved in decreased insulin- and IGF-1-stimul ated muscle metabolism during aging.