Proteolysis in skeletal muscle and whole body in response to euglycemic hyperinsulinemia in normal adults

Abstract

To simultaneously assess the relative antiproteolytic effect of insulin on both skeletal muscle and in the whole body, phenylalanine rates of appearance (Ra; reflecting proteolysis) were measured across the leg (reflecting skeletal muscle) and in the whole body, utilizing a constant tracer infusion of [2H5]phenylalanine in the basal state and during euglycemic hyperinsulinemia (2,600 microU/ml) in seven normal adults. Phenylalanine Ra in the leg was significantly decreased during hyperinsulinemia (6.11 +/- 0.83 vs 3.59 +/- 0.70 mumol/min, P less than 0.001). In contrast, leg phenylalanine rate of utilization (Rd) was not significantly changed (4.88 +/- 0.77 vs. 3.86 +/- 0.92 mumol/min). Phenylalanine Ra in the whole body was significantly decreased during hyperinsulinemia (49.4 +/- 2.2 vs. 41.9 +/- 2.3 mumol/min, P less than 0.001). However, phenylalanine release was suppressed to a significantly greater degree in release was suppressed to a significantly greater degree in the leg than in the whole body during hyperinsulinemia (43 +/- 7 vs. 15 +/- 2%, P less than 0.01). These results suggest that insulin suppresses proteolysis in the whole body and in skeletal muscle, even in the face of hypoaminoacidemia. In addition, the substantially greater degree of suppression of proteolysis by insulin in skeletal muscle compared with the whole body suggests that, at least under these conditions, insulin may have a greater antiproteolytic effect on skeletal muscle compared with other tissues.

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

“…These results are also supported by other studies [17, 20, Louard et al(a) 1992 [19] Fryburg et al 1995 [26] Timmerman et al (1b) 28-31, 34, 44]. In all healthy human studies where AA availability has been reduced, MPS has been reduced or remained unchanged [18,19,37,45,46], even in the presence of supraphysiological concentrations of insulin [18]. The meta-analysis of the 25 studies showed that insulin exerts its regulation of lean muscle mass principally via an anticatabolic effect in reducing MPB.…”

“…The role of insulin in adult human skeletal muscle is more complex and subject to interplay between other factors such as AA availability, muscle blood flow and microvascular recruitment [16,17]. This has led to various studies reporting opposing conclusions when it comes to the relationship between insulin and human skeletal muscle protein turnover [16][17][18][19][20][21][22]. We therefore undertook a systematic review and meta-analysis in an attempt to clarify the role of insulin in regulating muscle metabolism in humans.…”

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

“…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.…”

Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation

“…[8][9][10]20,21 In the pediatric population, one previous study measured the effects of insulin on protein metabolism in a cohort of 4 extremely low-birth-weight neonates. 22 The investigators showed a 20% reduction in protein breakdown, although this was associated with a corresponding decrease in protein synthetic rate.…”