Sodium valproate (VPA) reduces gluconeogenesis in type 2 diabetic rats. (A,B) Blood glucose levels increased 1 and 2 h after re-feeding in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an effect that was ameliorated by VPA administration; (C) Glycogen accumulation was analyzed by periodic acid–Schiff (PAS) staining of liver tissues. Representative images show the effect of VPA administration on glycogen accumulation in liver tissues (n = 6, scale bar = 50 μm); Expression of gluconeogenic genes, such as glucose 6-phosphatase ((D), G6p), fructose-1, 6-bisphosphatase (E, Fbp), phosphoenolpyruvate carboxykinase ((F), Pck1); and pyruvate carboxylase ((G), Pc) was quantified by reverse transcription-quantitative PCR. VPA administration decreased the expression of gluconeogenic genes in OLETF rats. Foxo1 mRNA was not significantly different between Long-Evans Tokushima Otsuka (LETO) and OLETF rats regardless of VPA treatment (H). The graphs show the mean ± standard error of mean (SEM) of six independent experiments. (* p < 0.05, ** p < 0.01 vs. Long-Evans Tokushima Otsuka (LETO) rats; #
p < 0.05 vs. OLETF vehicle).