Effect of systemic hyperinsulinemia on amino acid flux across human legs in postabsorptive state

Abstract

The effect of physiological hyperinsulinemia (approximately 110 mU/l) on leg tissue protein balance was investigated in eight weight-stable healthy individuals. A primed constant infusion of L-[U-14C]tyrosine was used to measure the disposal and release of tyrosine across the leg before and during 2 h of euglycemic clamp studies. The leg exchange of 3-methyl-L-histidine (3-MH) and all amino acids in blood were measured before and during insulinization, including the muscle tissue content of amino acids. Hyperinsulinemia decreased whole body tyrosine flux from 52 +/- 2 to 35 +/- 1 mumol/min (P less than 0.0001), whereas neither disposal (53 +/- 9 vs. 45 +/- 9 nmol.min-1.100 g-1) nor release of tyrosine across the leg (76 +/- 11 vs. 66 +/- 10 nmol X min-1 X 100 g-1) was significantly influenced. The arterial concentration and the leg exchange of 3-MH were not significantly affected by 2 h of hyperinsulinemia, but the sum of all amino acids declined significantly. The net leg balance of tyrosine was not affected at all by hyperinsulinemia, whereas the balance of the branched-chain amino acids and methionine were switched from efflux toward influx. Phenylalanine efflux from the leg only showed a trend to a significant effect by insulin. The muscle tissue concentration of six individual amino acids decreased significantly during hyperinsulinemia, particularly the branched-chain amino acids. The leg exchange of glucose, free fatty acids, and glycerol immediately changed significantly, as expected in response to insulinization.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…These findings are consistent with other studies that have reported a reduction in response to insulin [30,32,37,39,42,44] with the exception of three studies, which did not observe any significant change in MPB [45,47,48]. This might well be due to anabolic resistance to insulin in a relatively older study population and the presence of diabetes mellitus.…”

“…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.…”

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

“…The lack of effect of insulin on protein synthesis in the current study is in accord with most previous reports of insulin's action on human skeletal muscle during euaminoacidemia (10,11,13) or hypoaminoacidemia (12,42,43). In contrast to these is a recent report by Biolo et al suggesting that insulin stimulated leg muscle protein synthesis in a small number of healthy volunteers despite hypoaminoacidemia (14).…”

“…In most previous human studies, insulin promoted net muscle anabolism by decreasing proteolysis (10-13, 29, 44). Two studies, however, failed to show a significant effect of insulin on net muscle protein metabolism (42,43 ). In each case, insulin was infused systemically (causing hypoaminoacidemia) and the balances of several amino acids shifted positively.…”

MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review

“…In model 1, study arms were excluded in which the insulin administration was combined with amino acid co-interventions that raised plasma amino acid above basal levels and did not have a comparator group to correct for the increase in plasma amino acids Model 2 additionally excluded study arms in which amino acid levels were allowed to drop below basal levels (41,49,50,51,52,53,54,55). This criterion excluded an additional ten study arms compared with model 1, none of which reported an effect on muscle protein synthesis.…”