Conclusions
Protein-restricted FGR rats showed insulin resistance and altered insulin signaling in skeletal muscles after 12 weeks. However, we could not demonstrate the involvement of DNA methylation in this model.
Material and methods
To develop a protein-restricted FGR model, rats were fed a low-protein diet (7% protein) during the gestational period; rats fed a normal diet (20% protein) were used as controls. At 8 and 12 weeks of age, the pups were subjected to oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) to evaluate insulin resistance. At 12 weeks, the mRNA and protein levels of insulin signaling pathway molecules in the skeletal muscles were examined. DNA methylation of promoters was detected. DNA extracted from skeletal muscles was used as a template for methylation-specific PCR analysis of GLUT4.
Methods
To develop a protein-restricted FGR model, rats were fed a low-protein diet (7% protein) during the gestational period; rats fed a normal diet (20% protein) were used as controls. At 8 and 12 weeks of age, the pups were subjected to oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) to evaluate insulin resistance. At 12 weeks, the mRNA and protein levels of insulin signaling pathway molecules in the skeletal muscles were examined. DNA methylation of promoters was detected. DNA extracted from skeletal muscles was used as a template for methylation-specific PCR analysis of GLUT4.
Results
The body weight of FGR rats from birth to 8 weeks was significantly lower than that of the controls; no significant difference was observed between the groups at 12 weeks. In the OGTT and ITT, the incremental area under the curve (iAUC) was significantly higher in FGR rats than in the controls at 12 weeks. The mRNA and protein levels of Akt2 and GLUT4 in the plantar muscles were significantly lower in FGR rats than in the controls. GLUT4 methylation was comparable between the groups. Conclusions: Protein-restricted FGR rats showed insulin resistance and altered insulin signaling in skeletal muscles after 12 weeks. However, we could not demonstrate the involvement of DNA methylation in this model.