Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients

• Published in: Diabetologia Vol. 47; no. 5; pp. 917 - 925
• Main Authors: Debard, C., Laville, M., Berbe, V., Loizon, E., Guillet, C., Morio-Liondore, B., Boirie, Y., Vidal, H.
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.2004; Springer Nature B.V; Springer Verlag
• Subjects: Biochemistry, Molecular Biology; Biological and medical sciences; Blood Glucose - metabolism; Dehydrogenases; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology and metabolism; Endocrinopathies; Enzymes; Fatty acids; Fatty Acids - genetics; Fatty Acids - metabolism; Fatty Acids, Nonesterified - blood; Female; Food and Nutrition; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Human health and pathology; Humans; Hypotheses; Insulin resistance; Kinases; Life Sciences; Lipids; Male; Medical sciences; Metabolism; Middle Aged; Mitochondria; Models, Biological; Molecular biology; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Musculoskeletal system; Nutrition; Oxidation; Oxidation-Reduction; Phosphorylation; Proteins; Reference Values; Striated muscle. Tendons; Tissues and Organs; Triglycerides; Vertebrates: osteoarticular system, musculoskeletal system; Carbon-carbon ligases; Type 2 diabetes; Endocrinopathy; Human; Fatty acid oxidation; PGC1α; Enzyme; Adiponectin receptors; Lipids; Gene expression; Striated muscle; Fatty acids; Adiponectin; Polymerase chain reaction; Acetyl-CoA carboxylase; Real-time PCR; Ligases; Oxidation; Acetyl CoA carboxylase; Hyperinsulinaemic clamp; Biological receptor; PGC1 alpha; acetyl CoA carboxylase; fatty acid oxidation; real-time PCR; hyperinsulinaemic clamp; adiponectin receptors
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-004-1394-7

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. 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. 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. 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.