RAT TAIL SUSPENSION CAUSES A DECLINE IN INSULIN-RECEPTORS

Decreased muscular activity results in weakness and muscular atrophy. Coincident with this protein catabolic state is glucose intolerance an d hyperinsulinemia. Rats were tail suspended for 7 to 14 days to accom plish unloading of the hindlimbs. Insulin resistance was documented in these animals by a 14 day tail suspension-related 26% increase in ser um glucose in spite of a 253% increase in serum insulin concentration. Microsomal membranes were prepared from hindlimb muscles and specific binding of insulin and insulin-like growth factor I (IGF-I) were dete rmined in these membranes. Insulin binding was decreased by 27% at 7 d ays and by 21% at 14 days. In contrast, IGF-I binding was unchanged at 7 days and was increased by 24 % at 14 days. Liver membrane insulin r eceptors also had declined by 14 days of suspension, suggesting that t he change in insulin receptors was a generalized, humorally-mediated p henomenon. These data suggest that tail suspension in rats results in insulin resistance, hyperinsulinemia, a decline in insulin receptors i n liver and muscle, and a relative increase in muscle membrane IGF-I r eceptors. These data are consistent with the hypothesis that resistanc e to insulin's effects on protein metabolism in skeletal muscle may co ntribute to the protein catabolism associated with decreased muscular activity.