Effect of hyperinsulinemia on whole body and skeletal muscle leucine carbon kinetics in humans

Abstract

Data documenting the isolated effect of systemic hyperinsulinemia on whole body and skeletal muscle leucine carbon kinetics in humans are limited. Using steady-state [14C]leucine kinetics, 10 normal volunteers were studied in the baseline postabsorptive state and then under euglycemic, hyperinsulinemic (71 +/- 5 microU/ml), and euleucinemic conditions. Systemic hyperinsulinemia resulted in a significant decrease in whole body and forearm leucine rate of appearance (Ra) by 17 and 37%, respectively, (P less than 0.0003, 0.03), without a significant change in the nonoxidized rate of disappearance for either (P = 0.23, 0.66). The baseline contribution of total body skeletal muscle (TBSM) leucine Ra and rate of disappearance (Rd) to whole body leucine Ra and Rd was 27 +/- 6 and 24 +/- 5%, respectively. During hyperinsulinemia TBSM Ra decreased by 34%, whereas whole body Ra decreased by 16%. We conclude that the primary effect of insulin in the whole body and skeletal muscle is to decrease leucine release from protein without a significant effect on leucine incorporation into protein. This antiproteolytic effect of insulin is more pronounced in skeletal muscle than in other tissues in the body.

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

“…In a study by Fujita et al, exercising for 45 min successfully increased AA delivery and MPS compared with non-exercising controls, although exercise per se has acute anabolic effects on muscle MPS [21]. In some studies, however, increased AA delivery has not produced an insulininduced increase in MPS [16,43]. This is probably because the rises in AA delivery were very minimal and achieved mainly through increased blood flow, rather than an increased AA concentration.…”

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases

“…Those studies reporting an increase in muscle protein synthesis during hyperinsulinemia also show an increased amino acid delivery to the muscle (1, 2, 17, 25, 27, 42), whereas those reporting no change or a decrease in amino acid delivery also reported either a decrease or no change in muscle protein synthesis (11,16,23,24,27). The differences in amino acid delivery were primarily due to a general decrease in blood amino acid levels, which were dependent on the mode of insulin infusion (i.e., systemic vs. local) and/or the concomitant infusion of exogenous amino acids.…”

“…Several studies have reported an increase in human muscle protein synthesis in response to insulin (1,2,17,25,27,42). However, others have reported an inhibition of muscle proteolysis with no significant changes in muscle protein synthesis (11,14,16,23,24). We (44) have previously hypothesized that these different results might be explained by differences in amino acid availability.…”

“…Therefore, the studies that report an increase in muscle protein synthesis by insulin infusion also show an increased amino acid delivery to the muscle (1,2,15,17,25,27,42). Interestingly, most studies reporting no change in amino acid delivery and/or a reduction in blood amino acid concentrations with systemic insulin infusion also report that muscle proteolysis is inhibited (11,16,23,24).We hypothesized that insulin and nutritional energy stimulate skeletal muscle protein synthesis provided that blood amino acid availability is not reduced. To test our hypothesis, we examined the differential effects of an amino acid-lowering systemic insulin infusion with a high-energy clamp (hyperglycemic hyperlipidemic) vs. a local insulin infusion in the femoral artery with a low-energy euglycemic clamp that did not induce major decreases in blood amino acid concentrations.…”

“…Therefore, the studies that report an increase in muscle protein synthesis by insulin infusion also show an increased amino acid delivery to the muscle (1,2,15,17,25,27,42). Interestingly, most studies reporting no change in amino acid delivery and/or a reduction in blood amino acid concentrations with systemic insulin infusion also report that muscle proteolysis is inhibited (11,16,23,24).…”