At birth, the endocrine pancreas becomes more directly involved in the control of glycaemia than in utero. However, compared with other tissues, relatively little is known about the maturational changes that occur in the fetal endocrine pancreas in preparation for extrauterine life. This study examined the pancreatic β-cell response to exogenous administration of glucose and arginine in fetal horses with respect to their gestational age and concentration of cortisol, the hormone responsible for prepartum maturation of other fetal tissues. Glucose administration had no effect on fetal insulin secretion between 175 and 230 days of gestation but evoked a rapid insulin response in fetuses closer to term (290–327 days). In late gestation, the β-cell response was more rapid and greater in magnitude in fetuses with basal cortisol levels higher than 15 ng/ml than in those with lower cortisol values at the time of glucose administration. The fetal β-cell response to arginine was unaffected by the rise in fetal plasma cortisol towards term. These findings show that there are maturational changes in pancreatic β-cell function in fetal horses as cortisol levels rise close to term. Primarily, these prepartum maturational changes were in the mechanisms of glucose-stimulated insulin secretion, which would enable the β cells to regulate glycaemia at the higher glucose levels observed postnatally.
A L Fowden, D S Gardner, J C Ousey, D A Giussani and A J Forhead
K L Franko, D A Giussani, A J Forhead and A L Fowden
Fetal glucocorticoids have an important role in the pre-partum maturation of physiological systems essential for neonatal survival such as glucogenesis. Consequently, in clinical practice, synthetic glucocorticoids, like dexamethasone, are given routinely to pregnant women threatened with pre-term delivery to improve the viability of their infants. However, little is known about the effects of maternal dexamethasone treatment on the glucogenic capacity of either the fetus or mother. This study investigated the effects of dexamethasone treatment using a clinically relevant dose and regime on glycogen deposition and the activities of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and kidney of pregnant ewes and their fetuses, and of non-pregnant ewes. Dexamethasone administration increased the glycogen content of both the fetal and adult liver within 36 h of beginning treatment. It also increased G6Pase activity in the liver and kidney of the fetuses but not of their mothers or the non-pregnant ewes. Neither hepatic nor renal PEPCK activity was affected by dexamethasone in any group of animals. These changes in glycogen content and G6Pase activity were accompanied by rises in the plasma glucose and insulin concentrations and by a fall in the plasma cortisol level in the fetus and both groups of adult animals. In addition, dexamethasone treatment raised fetal plasma tri-iodothyronine (T3) concentrations and reduced maternal levels of plasma T3 and thyroxine, but had no effect on thyroid hormone concentrations in the non-pregnant ewes. These findings show that maternal dexamethasone treatment increases the glucogenic capacity of both the mother and fetus and has major implications for glucose availability both before and after birth.