Failure of Insulin Infusion to Stimulate Fractional Muscle Protein Synthesis in Type I Diabetic Patients: Anabolic Effect of Insulin and Decreased Proteolysis

We evaluated the influence of insulin on fractional mixed skeletal muscle protein synthesis (FMPS) in eight type I (insulin-dependent) diabetic patients in the postabsorptive state. FMPS was calculated from the increment in [¹³C]leucine in mixed skeletal muscle protein obtained by serial percutaneous needle biopsy during a continuous 8-h intravenous infusion of L-[¹³C]leucine. We used the plasma [¹³C]α-aketoisocaproate (representing intracellular leucine labeling) as the precursor pool of protein synthesis for our calculations. FMPS during the insulin treatment (0.0472 ± 0.0046%/h; plasma glucose 4.6 + 1.0 mM) was not different from FMPS during insulin deprivation (0.0499 ±0.0046%/h; plasma glucose 16.4 + 0.5 mM). Using plasma [¹³C]-α-ketoisocaproate at isotopic plateau for calculation of leucine flux and as the precursor for leucine oxidation, we further confirmed the findings of our group and others that insulin treatment decreases leucine flux, leucine oxidation, and the nonoxidative portion of leucine flux. Our data on direct measurement of FMPS provide further evidence that the anabolic effect of insulin in the postabsorptive type I diabetic patient is mediated via reduction of proteolysis rather than by increasing protein synthesis.