More important than expression levels of gluconeogenic enzymes is the capacity to produce glucose. In a study with isolated hepatocytes from PPARα −/− mice, glucose production from pyruvate was not significantly altered [23], but this was contradicted by Le May et al. who found a 20% reduction in gluconeogenesis from lactate/pyruvate in PPARα −/− hepatocytes [24]. The rate of de novo synthesized G6P and hepatic G6P levels were not different in 15 hours fasted PPARα −/− mice as compared with wild type mice [21]. However, the rate of G6P towards plasma glucose was diminished, while synthesis of uridine diphosphate glucose (UDP-glucose), and thus glycogen formation was higher [21], which could contribute to fasting hypoglycemia. This was in line with decreased hepatic glucose production (HGP) in fasted PPARα −/− mice [22]. The regulation of HGP from pyruvate/lactate in PPARα −/− mice during the physiologic situation of a moderate overnight fast (17 hours) and refeeding (5 hours) was studied more in detail using 13C-mass isotopomer distribution analysis (MIDA) by Xu et al. [20]. In PPARα −/− mice, decreased HGP from lactate was observed in the fed as well as in the fasted state [20].
