Abstract
Carbohydrate metabolism in the liver of the laboratory rat immediately before and after birth has been shown to be regulated by the hepatic adrenergic system. 125I-iodopindolol was used to characterise the beta-adrenoceptor population of liver membranes prepared from fetal and neonatal rats. The receptors were predominantly of the beta2-subtype. The dissociation constant of this radioligand (about 75pM) was not significantly different when membranes from animals of different ages were used, indicating that the type and subtype of receptors being labelled did not change with age. However, the size of the beta-adrenoceptor population did vary with age and reached a maximum in membranes isolated from term fetal rats. Hepatocytes were isolated from rats during the perinatal period and incubated with various adrenergic agents. Both glucose production and glycogen breakdown in freshly isolated hepatocytes were shown to be stimulated by adrenergic agonists. The use of adrenoceptor type- and subtype-specific agents confirmed that adrenergic modulation of carbohydrate metabolism in these cells was beta2-mediated. When hepatocytes were isolated from term fetuses of gestationally diabetic dams, glucose production and glycogen breakdown in these cells was shown to be resistant to adrenergic action. Adrenaline administered in vivo to newly-delivered rats was shown to increase plasma glucose and lactate concentrations and to decrease liver glycogen content at two hours after delivery. At appropriate doses, adrenaline prevented the hypoglycaemia normally seen in the hours immediately following birth in the rat. Adrenergic antagonists, when administered intraperitoneally immediately after delivery, prevented the natural increase in plasma glucose concentration at three hours post partum. The beta-adrenergic antagonist propranolol was more effective than the a-adrenergic antagonist phentolamine. These findings support activation of the adrenergic system as an essential factor in the mechanism for recovery from postnatal hypoglycaemia in the laboratory rat.