EXTREME HYPERINSULINEMIA UNMASKS INSULINS EFFECT TO STIMULATE PROTEIN-SYNTHESIS IN THE HUMAN FOREARM

Insulin clearly stimulates skeletal muscle protein synthesis in vitro. Surprisingly, this effect has been difficult to reproduce in vivo. As in vitro studies have typically used much higher insulin concentratio ns than in vivo studies, we examined whether these concentration diffe rences could explain the discrepancy between in vitro and in vivo obse rvations. In 14 healthy volunteers, we raised forearm insulin concentr ations 1,000-fold above basal levels while maintaining euglycemia for 4 h. Amino acids (AA) were given to either maintain basal arterial (n = 4) or venous plasma (n = 6) AA or increment arterial plasma AA by 10 0% (n = 4) in the forearm. We measured forearm muscle glucose, lactate , oxygen, phenylalanine balance, and [H-3]phenylalanine kinetics at ba seline and at 4 h of insulin infusion. Extreme hyperinsulinemia strong ly reversed postabsorptive muscle's phenylalanine balance from a net r elease to an uptake (P < 0.001). This marked anabolic effect resulted from a dramatic stimulation of protein synthesis (P < 0.01) and a mode st decline in protein degradation. Furthermore, this effect was seen e ven when basal arterial or venous aminoacidemia was maintained. With m arked hyperinsulinemia, protein synthesis increased further when plasm a AA concentrations were also increased (P < 0.05). Forearm blood flow rose at least twofold with the combined insulin and AA infusion (P < 0.01), and this was consistent in all groups. These results demonstrat e an effect of high concentrations of insulin to markedly stimulate mu scle protein synthesis in vivo in adults, even when AA concentrations are not increased. This is similar to prior in vitro reports but disti nct from physiological hyperinsulinemia in vivo where stimulation of p rotein synthesis does not occur. Therefore, the current findings sugge st that the differences in insulin concentrations used in prior studie s may largely explain the previously reported discrepancy between insu lin action on protein synthesis in adult muscle in vivo vs. in vitro.