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coactivator-1
of fibres in the soleus muscle of Zucker diabetic fatty rats1 Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan 2 Laboratory of Metabolism5 Laboratory of Neurochemistry, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan 3 Diabetic Center, Tsunashimakai-Kosei Hospital, Himeji, Japan 4 Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
We have reported that a change in muscle fibre type distribution is present in two strains of diabetic rats (Otsuka LongEvans Tokushima Fatty and Goto-Kakizaki rats). In this study, we determined whether the change in soleus muscle fibre type distribution was caused by diabetes, using obese, diabetic (Zucker diabetic fatty, ZDF), obese, non-diabetic (Zucker fatty, ZF) and non-diabetic, non-obese rats (Zucker lean, ZL). Moreover, we investigated whether the gene expression levels of metabolic key molecules, namely the transcriptional factors of metabolic genes, exemplified by peroxisome proliferator-activated receptor-
coactivator-1
(PGC-1
), and the oxidative enzymes in mitochondria, exemplified by succinate dehydrogenase (SDH), were changed in type I and II muscle fibres in each type of rat, using the new technique of laser capture microdissection (LCM). Both plasma glucose and glucosylated haemoglobin levels were significantly higher in ZDF than in ZL and ZF rats. A lower percentage of type IIA fibres was observed in the muscles of ZDF rats than in those of ZL and ZF rats. The mRNA expression levels of SDH in type II fibres and of PGC-1
in type I fibres were significantly lower in ZDF than in ZL and ZF rats as assessed by LCM and real-time PCR analysis. We have shown, for the first time, that a lower percentage of type IIA fibres was observed in ZDF rats. We have also discovered that the expression levels of the oxidative metabolism-related genes, PGC-1
and SDH, decreased in type I and type II fibres, respectively, of ZDF rats.
(Received 13 August 2006;
accepted after revision 6 December 2006; first published online 7 December 2006)
Corresponding author T. Adachi: Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. Email: adachi-tet{at}umin.ac.jf
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