title: Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion.
abstract: OBJECTIVE
  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
  Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration.
authors.affiliation: Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Cettour-Rose
authors.forename: C
authors.initials: C
authors.lastname: Theander-Carrillo
authors.forename: C
authors.initials: C
authors.lastname: Asensio
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
authors.forename: A G
authors.initials: AG
authors.lastname: Burger
authors.forename: C A
authors.initials: CA
authors.lastname: Meier
authors.forename: F
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015870:Gene Expression / Q000235:genetics; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006729:Hormones, Ectopic / Q000235:genetics; D006980:Hyperthyroidism / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011441:Propylthiouracil; D051381:Rats; D017208:Rats, Wistar; D052243:Resistin; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014280:Triglycerides / Q000032:analysis / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000494:pharmacology; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D001786:Blood Glucose; D002334:Carnitine O-Palmitoyltransferase; D005230:Fatty Acids, Nonesterified; D005947:Glucose; D006729:Hormones, Ectopic; D007328:Insulin; D007453:Iodide Peroxidase; D020738:Leptin; D011441:Propylthiouracil; D052243:Resistin; D013972:Thyrotropin; D013974:Thyroxine; D014280:Triglycerides; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D000097564:Iodothyronine Deiodinase Type II; C499622:Retn protein, rat; C109812:iodothyronine deiodinase type I