Review article: Regulation of glucose production with special attention to nonclassical regulatory mechanisms: a review

Hepatic glycogenolysis and gluconeogenesis are essential processes for the prevention of hypoglycemia during short-term starvation. As has been calculated from stable isotope studies, gluconeogenesis accounts for approximately 35% to 50% of total basal glucose production, glycogenolysis for the other 50% to 65%. In long-term starvation, the kidney also contributes to glucose production by gluconeogenesis. Glucose production is regulated by the interaction of different regulatory mechanisms, eg, by glucoregulatory hormones, glucose itself, and gluconeogenic substrates. In the last decades, more insight has been gained into the importance of the autonomous nervous system and the existence of an extensive paracrine network in the liver that seems to exert a potent glucoregulatory role as well. This review is focused on the regulation of hepatic glucose production by the autonomous nervous system and the paracrine network, with special emphasis on studies carried out in human subjects