Glucose-lowering effect of β-phenylpyruvate in neonatal mice: A possible mechanism for phenylketonuria-related neurodegenerative changes

Following β-phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with β-phenylpyruvate and their blood glucose determined and brain histology assessed. β-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent β-phenylpyruvate-induced hypoglycemic events.