Dose-response curves of effects of insulin on leucine kinetics in humans

Abstract

To determine the effects of physiological and pharmacological insulin concentrations on leucine-carbon kinetics in vivo, eight postabsorptive normal volunteers were infused with L-[4,5-3H]leucine and alpha-[1-14C]ketoisocaproate (KIC). Insulin concentrations were sequentially raised from 8 +/- 1 to 43 +/- 6 and 101 +/- 14 and to 1,487 +/- 190 microU/ml, while maintaining euglycemia with adequate glucose infusions. At the end of each 140-min insulin-infusion period, steady-state estimates of leucine and KIC rates of appearance (Ra), KIC (approximately leucine-carbon) oxidation, nonoxidized leucine-carbon flux [an index of leucine incorporation into protein (Leu----P)], and leucine and KIC interconversion rates were obtained. After the three insulin infusions, leucine Ra decreased by a maximum of approximately 20%. KIC Ra decreased by a maximum of approximately 50%. The sum of leucine plus KIC Ra in the basal state was 2.59 +/- 0.24 mumol X kg-1 X min-1 and decreased by approximately 30% at the maximal insulin concentrations. KIC oxidation decreased by a maximum of approximately 65%. Leu----P did not increase after hyperinsulinemia. Interconversion rates were promptly and markedly suppressed by 50-70%. Leucine clearance increased by approximately 120%. We conclude that euglycemic hyperinsulinemia, at physiological and pharmacological concentrations, decreased leucine and KIC concentrations, leucine-carbon turnover and oxidation, and leucine and KIC interconversions in a dose-dependent manner in vivo.

Insulin Is Protein-Anabolic in Chronic Renal Failure Patients

“…In normal subjects, insulin suppresses proteolysis in a dosedependent manner (17,23). Castellino et al (9) and Tessari et al (17) found that insulin also suppresses leucine oxidation.…”

“…Total infusion time was 540 min. Tessari et al (17) used similar successive short infusion protocol to study the dose-response relationship of insulin on leucine kinetics in humans. Solutions were infused through a venous catheter in one forearm, and blood samples were collected from a vein in the contralateral arm.…”

Action of GH on skeletal muscle function: molecular and metabolic mechanisms

“…Human studies employing recombinant IGF1 provide the strongest evidence that circulating IGF1 is anabolic. IGF1 enhances protein anabolism by reducing the rate of proteolysis, an action similar to that of insulin (Fukagawa et al 1985, Tessari et al 1986, Jacob et al 1989. When IGF1 is infused in rats, it leads to a reduction in protein breakdown without any change in protein synthesis (Jacob et al 1989).…”

Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men

“…Although the conventional clamp achieves hyperinsulinemia within the postprandial range, it does not replicate postmeal circulating metabolite concentrations. Indeed, it generates hypoaminoacidemia by insulin inhibition of protein catabolism, thereby preventing the testing of insulin sensitivity of protein anabolism by decreasing amino acid (AA) availability (6,38,46). Since insulin stimulation of protein synthesis and inhibition of proteolysis are unambiguously established in vitro, and abnormal protein metabolism occurs in both type 1 (45) and type 2 diabetes (17,19) we have previously used an hyperinsulinemic, euglycemic, isoaminoacidemic clamp (8) to explore whole body protein turnover.…”