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Response of Leucine Metabolism to Hyperinsulinemia in Hypothyroid Patients before and after Thyroxine Replacement¹

Centre de Recherche en Nutrition Humaine d’Auvergne: Unité d’Etude du Métabolisme Azoté, Institut National de la Recherche Agronomique, Centre de Clermont-Ferrand (C.R., P.C., G.B., J.P., C.C., J.G.), 63122 Saint-Genès Champanelle; Service d’Endocrinologie et Maladies Métaboliques CHU de Clermont-Ferrand (C.R., I.T., A.F., C.B., P.T.), B.P. 69, 63003 Clermont-Ferrand cedex; Service de Médecine nucléaire in vivo (C.D.), centre Jean Perrin 63003 Clermont-Ferrand; and Service de Médecine Interne (P.B.), Centre Hospitalier 03000 Moulins, France

We have investigated the effect of hypothyroidism and insulin on protein metabolism in humans. Six hypothyroid patients were studied in a postabsorptive state before and after 5 months of regular treatment for hypothyroidism (153 ± 17 µg/day of L-T₄). The effect of insulin was assessed under hyperinsulinemic euglycemic and eukalemic conditions. Insulin was infused for 140 min at 0.0063 ± 0.0002 nmol/kg·min. An amino acid infusion was used to blunt insulin-induced hypoaminoacidemia. Whole body protein turnover was measured using L-[1-¹³C] leucine. When compared to L-T₄-induced subclinical thyrotoxic state, hypothyroidism induced a significant decrease (P < 0.05) in leucine endogenous appearance rate (a reflection of proteolysis; 0.89 ± 0.09 vs. 1.33 ± 0.05 µmol/kg·min), oxidation (0.19 ± 0.02 vs. 0.25 ± 0.03 µmol/kg·min), and nonoxidative disposal (a reflection of protein synthesis; 0.87 ± 0.11 vs. 1.30 ± 0.05 µmol/kg·min). Insulin lowered proteolysis during both the subclinical thyrotoxic and hypothyroid states. Hypothyroidism impaired the antiproteolytic effects of insulin. Thyroid hormones are, therefore, essential for the normal antiproteolytic action of insulin.

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