Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms.

Abstract

Insulin inhibits proteolysis in human muscle thereby increasing protein anabolism. In contrast, IGF-I promotes muscle protein anabolism principally by stimulating protein synthesis. As increases or decreases of plasma amino acids may affect protein turnover in muscle and also alter the muscle's response to insulin and/or IGF-I, this study was designed to examine the effects of insulin and IGF-I on human muscle protein turnover during hyperaminoacidemia. We measured phenylalanine balance and [3HI -phenylalanine kinetics in both forearms of 22 postabsorptive adults during a continuous [3HIphenylalanine infusion.Measurements were made basally and at 3 and 6 h after beginning a systemic infusion of a balanced amino acid mixture that raised arterial phenylalanine concentration about twofold. Throughout the 6 h, 10 subjects received insulin locally (0.035 mU/min per kg) into one brachial artery while 12 other subjects were given intraaterial IGF-I (100 ng/min per kg) to raise insulin or IGF-I concentrations, respectively, in the infused arm. The contralateral arm in each study served as a simultaneous control for the effects of amino acids (aa) alone.Glucose uptake and lactate release increased in the insulin-and IGF-I-infused forearms (P < 0.01) but did not change in the contralateral (aa alone) forearm in either study. In the aa alone arm in both studies, hyperaminoacidemia reversed the postabsorptive net phenylalanine release by muscle to a net uptake (P < 0.025, for each) due to a stimulation of muscle protein synthesis. In the hormoneinfused arms, the addition of either insulin or IGF-I promoted greater positive shifts in phenylalanine balance than the aa alone arm (P < 0.01). With insulin, the enhanced anabolism was due to inhibition of protein degradation (P < 0.02), whereas IGF-I augmented anabolism by a further stimulation of protein synthesis above aa alone (P < 0.02). We conclude that: (a) hyperaminoacidemia specifically stimulates muscle protein synthesis; (b) insulin, even with hyperaminoacidemia, improves muscle protein balance solely by inhibiting proteolysis; and (c) hyperaminoacidemia combined with IGF-I enhances protein synthesis more

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

“…Insulin had no effect on MPS when AA delivery was unchanged from baseline. 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].…”

“…Meta-analysis of study characteristics A total of 13 articles [16,[19][20][21][24][25][26][27][28][29][30][31][32], containing 25 experimental studies using different insulin concentrations, were identified for inclusion in the meta-analysis (Table 1); all analysed the effect of insulin on both MPS and MPB (Table 1). A total of 173 individuals were included in these studies.…”

IGF-I, IGF-I-binding proteins and GH-binding protein in malnourished elderly patients with inflammation receiving refeeding therapy

“…IGF-I has strong insulin-like metabolic effects (13). In particular, IGF-I stimulates protein synthesis (38) and inhibits protein breakdown (39); it is an anabolic hormone. Plasma IGF-I levels are regulated by nutrition, via plasma insulin levels and protein and calorie intake (12).…”

Muscle amino acid pattern in obese rats

“…24 Obese animals, both diet induced and genetically, are hyperinsulinaemic. 25±27 In the diet-obese group, the increase in amino acid availability, due to increased arterial blood concentrations and the increased blood ow, could generate a favourable gradient that facilitates muscle uptake of many amino acids, 28 mainly Ala, Val and Arg (the relative extraction ratio for these amino acids were: 8, 24 and 24% respectively). The uptake of Ala could be favoured by the insulin induction of the transport system A 24 although this pattern may not be followed by other amino acid transport systems, since the uptake relates amino acid availability with a dubious activation of other selective transport systems.…”