Impaired expression of NADH dehydrogenase subunit 1 and PPARgamma coactivator-1 in skeletal muscle of ZDF rats: restoration by troglitazone
| Autor: | Mireia, Jové, Joel, Salla, Anna, Planavila, Agatha, Cabrero, Liliane, Michalik, Walter, Wahli, Juan C, Laguna, Manuel, Vázquez-Carrera |
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| Rok vydání: | 2003 |
| Předmět: |
Blood Glucose
Male Down-Regulation Membrane Transport Proteins Receptors Cytoplasmic and Nuclear NADH Dehydrogenase DNA Mitochondrial Ion Channels Rats Rats Zucker Mitochondrial Proteins Troglitazone Animals Thiazolidinediones Uncoupling Protein 2 RNA Messenger Chromans Muscle Skeletal Transcription Factors |
| Zdroj: | Journal of lipid research. 45(1) |
| ISSN: | 0022-2275 |
| Popis: | Type 2 diabetes has been related to a decrease of mitochondrial DNA (mtDNA) content. In this study, we show increased expression of the peroxisome proliferator-activated receptor-alpha (PPARalpha) and its target genes involved in fatty acid metabolism in skeletal muscle of Zucker Diabetic Fatty (ZDF) (fa/fa) rats. In contrast, the mRNA levels of genes involved in glucose transport and utilization (GLUT4 and phosphofructokinase) were decreased, whereas the expression of pyruvate dehydrogenase kinase 4 (PDK-4), which suppresses glucose oxidation, was increased. The shift from glucose to fatty acids as the source of energy in skeletal muscle of ZDF rats was accompanied by a reduction of subunit 1 of complex I (NADH dehydrogenase subunit 1, ND1) and subunit II of complex IV (cytochrome c oxidase II, COII), two genes of the electronic transport chain encoded by mtDNA. The transcript levels of PPARgamma Coactivator 1 (PGC-1) showed a significant reduction. Treatment with troglitazone (30 mg/kg/day) for 15 days reduced insulin values and reversed the increase in PDK-4 mRNA levels, suggesting improved insulin sensitivity. In addition, troglitazone treatment restored ND1 and PGC-1 expression in skeletal muscle. These results suggest that troglitazone may avoid mitochondrial metabolic derangement during the development of diabetes mellitus 2 in skeletal muscle. |
| Databáze: | OpenAIRE |
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