Glucose homeostasis in the perinatal period: the critical role of pancreatic hormones and exogenous substrates in the rat.

Abstract

Birth in most mammalian species is characterized by an abrupt change from a high carbohydrate and low fat diet to a high fat and low carbohydrate diet. As the supply of glucose from the milk is not sufficient to cover the glucose needs of several tissues (such as the brain and the red blood cells) and as liver glycogen stores are exhausted within 12 hours of delivery, the newborn rapidly becomes dependent on its capacity for efficient gluconeogenesis. Among the factors that control the appearance of gluconeogenesis in the liver of the neonate, the pancreatic hormones play a crucial role. Studies in the rat have shown that the rise in plasma glucagon and the fall in plasma insulin which occur immediately after birth are the main determinants of the appearance of liver phosphoenolpyruvate carboxykinase (GTP), the rate-limiting enzyme of glyconeogenesis in this species. However, when this enzyme has reached its adult values in the liver 12 to 24 hours after birth, other factors involved in the regulation of hepatic gluconeogenesis. In order for it to maintain a high rate of gluconeogenesis the liver of the neonate must be supplied with sufficient amounts of gluconeogenic precursors and of non-esterified fatty acids. Studies in the rat have shown that active fatty acid oxidation is necessary to support gluconeogenesis by providing essential cofactors such as acetyl-CoA and NADH. The relevance of these studies for the understanding of neonatal glucose homeostasis in man is discussed.