Response of leucine metabolism to hyperinsulinemia in hypothyroid patientsbefore and after thyroxine replacement

We have investigated the effect of hypothyroidism and insulin on protein me tabolism in humans. Six hypothyroid patients were studied in a postabsorpti ve state before and after 5 months of regular treatment for hypothyroidism (153 +/- 17 mu g/day of L-T,). The effect of insulin was assessed under hyp erinsulinemic euglycemic and eukalemic conditions. Insulin was infused for 140 min at 0.0063 +/- 0.0002 nmol/kg.min. An amino acid infusion was used t o blunt insulin-induced hypoaminoacidemia. Whole body protein turnover was measured using L-[1-C-13] leucine. When compared to L-T-4-induced subclinic al thyrotoxic state, hypothyroidism induced a significant decrease (P < 0.0 5) in leucine endogenous appearance rate (a reflection of proteolysis; 0.89 +/- 0.09 us. 1.33 +/- 0.05 mu mol/kg min), oxidation (0.19 +/- 0.02 vs. 0. 25 +/- 0.03 mu mol/kg.min), and nonoxidative disposal (a reflection of prot ein synthesis; 0.87 +/- 0.11 vs. 1.30 +/- 0.05 mu mol/kg min). Insulin lowe red proteolysis during both the subclinical thyrotoxic and hypothyroid stat es. Hypothyroidism impaired the antiproteolytic effects of insulin. Thyroid hormones are, therefore, essential for the normal antiproteolytic action o f insulin.