PROTEIN DYNAMICS IN WHOLE-BODY AND IN SPLANCHNIC AND LEG TISSUES IN TYPE-I DIABETIC-PATIENTS

To elucidate the mechanism of insulin's anticatabolic effect in humans , protein dynamics were evaluated in the whole-body, splanchnic, and l eg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate ami no acid models (leucine and phenylalanine). L-(1-C-13,N-15) leucine, L -(ring-H-2(5))phenylalanine, and L-(ring-H-2(2)) tyrosine were infused intravenously, and isotopic enrichments of [1-C-13,N-15]-leucine, (C- 13)leucine, (C-13)ketoisocaproate, (H-2(5))phenylalanine, [2H(4)]tyros ine, (H-2(2))tyrosine, and (CO2)-C-13 were measured in arterial, hepat ic vein, and femoral vein samples, Whole-body leucine flux, phenylalan ine flux, and tyrosine flux were decreased(< 0.01) by insulin treatmen t, indicating an inhibition of protein breakdown, Moreover, insulin de creased(< 0.05) the rates of leucine oxidation and leucine transaminat ion (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01), Insulin also reduced (< 0.01) whole-b ody protein synthesis estimated from both the leucine model (nonoxidat ive leucine disposal) and the phenylalanine model (disposal of phenyla lanine not accounted by its conversion to tyrosine), Regional studies demonstrated that changes in whole body protein breakdown are accounte d for by changes in both splanchnic and leg tissues, The changes in wh ole-body protein synthesis were not associated with changes in skeleta l muscle (leg) protein synthesis but could be accounted for by the spl anchnic region, We conclude that though insulin decreases whole-body p rotein breakdown in patients with type I diabetes by inhibition of pro tein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the obse rved decrease in whole-body protein synthesis, Insulin also augmented anabolism by decreasing leucine transamination.