Insulin responsiveness of protein metabolism in vivo following bedrest in humans

To test the influence of bedrest on insulin regulation of leucine metabolism, six normal young men were subjected to a five-step hyperinsulinemic euglycemic clamp before and after 7 days of strict bedrest. A primed-constant infusion of [1-¹³C]leucine at 0.12 ± 0.02 μmol·kg^-1·min^-1 was used. Before bedrest, the basal rate of appearance (R(a)) of intracellular leucine and leucine oxidation were 2.79 ± 0.17 and 0.613 ± 0.070 μmol·kg^-1·min^-1, respectively. Insulin caused a dose-dependent reduction of the intracellular leucine R(a) and leucine oxidatin to a minimum of 1.64 ± 0.08 and 0.322 ± 0.039 μmol·kg^-1·min^-1, respectively in nonbedrested subjects (P < 0.001). Insulin also caused a dose-dependent reduction of plasma leucine concentration from 95 ± 4 to 38 ± 2 μmol/l (P < 0.001). After bedrest, subjects exhibited decreased glucose tolerance and increased endogenous insulin secretion, but basal and insulin-suppressed intracellular leucine R(a) and leucine oxidation rates were not different from control. Magnetic resonance imaging of the back and lower extremities revealed a 1-4% decrease in muscle volume and a 2-5% increase in fat volume secondary to bedrest. Bedrest also resulted in a negative nitrogen balance as compared with the control period, with an average cumulative loss of 6.3 g of nitrogen after 6 days. Urinary 3-methyl-L-histidine excretion was unchanged by bedrest. Thus because negative nitrogen balance and skeletal muscle atrophy occurred in six rested subjects in the absence of changes in the two indices of protein breakdown used in this study (3-methyl-L-histidine release and leucine release), it seems likely that muscle protein synthesis was inhibited.