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Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

Cettour-Rose, P. ; Theander-Carrillo, C. ; Asensio, C. ; Klein, M. ; Visser, T. ; Burger, A. ; Meier, C. ; Rohner-Jeanrenaud, F.

In: Diabetologia, 2005, vol. 48, no. 4, p. 624-633

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    Titre
    • Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion
    Auteur
    • Cettour-Rose, P.. Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Theander-Carrillo, C.. Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Asensio, C.. Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Klein, M.. Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Visser, T.. Internal Medicine III, Erasmus University Medical Center, Rotterdam, The Netherlands
    • Burger, A.. Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Meier, C.. Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    • Rohner-Jeanrenaud, F.. Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Diabetologia, 2005, vol. 48, no. 4, p. 624-633. Springer-Verlag; http://www.springer.de
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:315764
    Summary
    Aims/hypothesis: The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect. Methods: Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-d-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects. Results: Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulin-stimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content. Conclusions/interpretation: Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration