INSULIN ATTENUATES ATROPHY OF UNWEIGHTED SOLEUS MUSCLE BY AMPLIFIED INHIBITION OF PROTEIN-DEGRADATION

Unweighting atrophy of immature soleus muscle occurs rapidly over the first several days, followed by slower atrophy coinciding with increas ed sensitivity to insulin of in vitro protein metabolism. This study d etermined whether this increased sensitivity might account for the dim inution of atrophy after 3 days of tail-cast hindlimb suspension. The physiological significance of the increased response to insulin in unw eighted muscle was evaluated by analyzing in vivo protein metabolism f or day 3 (48 to 72 hours) and day 4 (72 to 96 hours) of unweighting in diabetic animals either injected with insulin or not treated. Soleus from nontreated diabetic animals showed a similar loss of protein duri ng day 3 (-16.2%) and day 4 (-14.5%) of unweighting, whereas muscle fr om insulin-treated animals showed rapid atrophy (-14.5%) during day 3 only, declining to just -3.1% the next day. Since fractional protein s ynthesis was similar for both day 3 (6.6%/d) and day 4 (7.0%/d) of unw eighting in insulin-treated animals, the reduction in protein loss mus t be accounted for by a slowing of protein degradation due to circulat ing insulin. Intramuscular (IM) injection of insulin (500 nmol/L) stim ulated in situ protein synthesis similarly in 4-day unweighted (+56%) and weight-bearing (+90%) soleus, even though unweighted muscle showed a greater in situ response of 2-deoxy-[H-3]glucose uptake to IM injec tion of either insulin (133 nmol/L) or insulin-like growth factor-I (I GF-I) (200 nmol/L) than control muscle, These findings suggest that un weighted muscle is selectively more responsive in vivo to insulin, and that the slower atrophy after 3 days of unweighting was due to an inc reased effect of insulin on inhibiting protein degradation. Copyright (C) 1997 by W.B. Saunders Company.