La gluconéogenèse - une voie métabolique essentielle au maintien de l'homéostasie glucidique du nouveau-né

Abstract

Birth is characterized by a dramatic change of nutrition, the fetal diet being rich in carbohydrates and poor in fat and the neonatal diet rich in fat and poor in carbohydrates. When the mother is normally fed, gluconeogenesis and fatty acid oxidation are absent or very low in the fetal liver and these metabolic pathways emerge after birth to reach adult values after 24 hours. Gluconeogenesis increases rapidly in the liver of newborn in parallel with the appearance of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of this metabolic pathway. The rise in plasma glucagon and the resulting increase in liver cAMP which occur immediately after birth are the factors which induce the transcription of the gene encoding PEPCK 'in the liver. Once liver PEPCK activity has reached adult value, i.e. 12 hours after birth, other factors are involved in the regulation of hepatic gluconeogenesis. Indeed, the supply of gluconeogenic susbtrates and of free fatty acids is of crucial importance to support a high rate of gluconeogenesis and to maintain normoglycemia in the newborn. In the liver, fatty acid oxidation provides essential co-factors (acetyl-CoA, NADH and ATP) to support gluconeogenesis. Similar mechanisms are operative in human newborn. An impaired secretion of glucagon or a defective hepatic fatty acid oxidation are likely to explain the frequent hypoglycemia observed in infants of diabetic mothers and in small-for-date neonates. Administration of oral triglycerides is an efficient mean to prevent hypoglycemia in these newborns.