title: Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients.
abstract: OBJECTIVE
  Defective oxidation of long-chain fatty acids is a feature of insulin resistance and Type 2 diabetes. Our aim was to compare the expression levels of the genes encoding the major proteins and enzymes of this pathway in skeletal muscle of healthy subjects and Type 2 diabetic patients.
  
  
  METHODS
  The basal and insulin-regulated mRNA concentration of 16 genes was quantified using real-time PCR in skeletal muscle biopsies taken before and at the end of a 3-hour hyperinsulinaemic-euglycaemic clamp in healthy lean subjects and in insulin-resistant obese patients with manifest Type 2 diabetes.
  
  
  RESULTS
  Acetyl CoA carboxylase-2 mRNA expression was increased 2.5-fold in the muscle of the diabetic patients. The expression of carnitine palmitoyl transferase-1, of the two adiponectin receptors and of genes involved in fatty acid transport and activation was not altered in diabetic patients. Hyperinsulinaemia for 3 hours increased the expression of several genes of fatty acid oxidation, including adiponectin receptor-1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. It also reduced pyruvate dehydrogenase 4 mRNA levels. The effects of insulin on gene expression were markedly altered in the muscle of Type 2 diabetic patients except for adiponectin receptor-1 and pyruvate dehydrogenase 4 mRNAs.
  
  
  CONCLUSIONS
  The expression of adiponectin receptors was not altered in the muscle of Type 2 diabetic patients. The observed overexpression of acetyl CoA carboxylase-2 is consistent with the hypothesis that increased skeletal muscle malonyl CoA concentrations in Type 2 diabetes may contribute to the inhibition of long-chain fatty acid oxidation.
authors.affiliation: Unit of Research INSERM U-449/INRA-1235 and Lyon Centre of Research in Human Nutrition, Faculty of Medicine R. Laennec, Université Claude Bernard, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Debard
authors.forename: M
authors.initials: M
authors.lastname: Laville
authors.forename: V
authors.initials: V
authors.lastname: Berbe
authors.forename: E
authors.initials: E
authors.lastname: Loizon
authors.forename: C
authors.initials: C
authors.lastname: Guillet
authors.forename: B
authors.initials: B
authors.lastname: Morio-Liondore
authors.forename: Y
authors.initials: Y
authors.lastname: Boirie
authors.forename: H
authors.initials: H
authors.lastname: Vidal
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D010084:Oxidation-Reduction; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D005947:Glucose