Abstract. To examine the protein anabolic actions of insulin in chronic renal failure, the authors measured four sets of whole body leucine fluxes during insulin alone and insulin with amino acid infusion in nine uremic patients before hemodialysis (B-HD). Seven were restudied 8 wk after initiation of maintenance hemodialysis (HD). Six normal subjects served as control (N). All values ( mol/kg/h, mean Ϯ SEM) are presented in the sequence of B-HD, HD, and N, and only P Ͻ 0.05 are listed. During Flux 1 (baseline), D (leucine release from body protein degradation) were 114 Ϯ 7, 126 Ϯ 4, and 116 Ϯ 6, respectively. C (leucine oxidation rates) were 18 Ϯ 2, 17 Ϯ 2, and 21 Ϯ 3, respectively. S (leucine disappearance into body protein [index of protein synthesis]) were 96 Ϯ 6, 107 Ϯ 4, and 94 Ϯ 4, respectively, and balances (net leucine flux into protein [values were negative during fasting]) were Ϫ18 Ϯ 2, Ϫ17 Ϯ 2, and Ϫ21 Ϯ 3, respectively. During Flux 2 (low-dose insulin infusion), D were 89 Ϯ 3, 98 Ϯ 6, and 94 Ϯ 5, respectively; C were 12 Ϯ 1, 11 Ϯ 2, and 18 Ϯ 1, respectively (P ϭ 0.02); S were 77 Ϯ 4, 87 Ϯ 5, and 76 Ϯ 5, respectively, and balances were Ϫ12 Ϯ 1, Ϫ11 Ϯ 2, and Ϫ18 Ϯ 1, respectively (P ϭ 0.02). During Flux 3 (high-dose insulin infusion): D were 77 Ϯ 3, 82 Ϯ 7, and 84 Ϯ 5, respectively; C were 9 Ϯ 1, 8 Ϯ 1, and 14 Ϯ 1, respectively (P ϭ 0.005); S were 68 Ϯ 4, 74 Ϯ 6, and 70 Ϯ 5, respectively, and balances were Ϫ9 Ϯ 1, Ϫ8 Ϯ 1, and Ϫ14 Ϯ 1, respectively (P ϭ 0.005). In Flux 4 (insulin infused with amino acids): D were 73 Ϯ 3, 107 Ϯ 18, and 85 Ϯ 7, respectively; C were 35 Ϯ 4, 29 Ϯ 5, and 39 Ϯ 3, respectively; S were 105 Ϯ 5, 145 Ϯ 15, and 113 Ϯ 6, respectively (P ϭ 0.02), and balances were 32 Ϯ 4, 38 Ϯ 5, and 27 Ϯ 3, respectively. These data show that B-HD and HD patients were as sensitive as normal subjects to the protein anabolic actions of insulin. Insulin alone reduced proteolysis and leucine oxidation, and insulin given with amino acids increased net protein synthesis.There is a prevailing view in the nephrology community that uremia is an insulin-resistant state. In reviews relating malnutrition to chronic renal failure (CRF), insulin resistance is invariably mentioned as a potential cause for the increase in protein catabolism (1-3). This perception is derived partially from the well-described phenomenon of impaired non-oxidative glucose disposal in uremic patients (4,5) and partially from findings of increased release and impaired incorporation of amino acids from and into tissue during insulin treatment in acute and chronic uremic rat models (6,7). Despite this general belief, there are few papers addressing insulin action on protein metabolism in CRF patients (8 -13). Whether uremia imparts insulin resistance and whether maintenance hemodialysis alters insulin sensitivity with regard to protein metabolism in humans is uncertain. Malnutrition is a pervasive problem in CRF patients (14 -16); it is therefore important to investigate whether insulin retains its anabolic function in this population.In ...