ABSTRACT
The ontogeny of glucose regulation was studied in the rat by measuring the levels of plasma glucose, tissue glucose and tissue glycogen from fetal day 15 (E15) to adulthood. Since insulin and adrenaline are important glucose regulators in the adult, we also tested the effects of these hormones on above variables. The main findings are the following: 1) Umbilical blood glucose was very low (25 mg/100 ml) from E15 to E19, increasing to 66 mg/ml by E21 but still below maternal levels (110 mg/100 ml). 2) Umbilical venous-arterial (VEN-ART) glucose differences were very small (1 mg/100 ml) from E15 to E17, increased to 6 mg/100 ml by E19, but dropped again becoming negative (-l5 mg/100 ml) just before birth when umbilical arterial blood glucose rose above venous blood glucose. 3) Glucose and glycogen concentrations rose drastically in liver towards the end of gestation. 4) Tissue glycogen and, to a much lesser degree, glucose, fell after birth to rise again in adulthood. 5) Insulin injection caused an increase in liver glycogen from E17 onwards, and also increased glycogen in brain and placenta on E19. However, insulin decreased glycogen in brain and kidney by E21. 6) Adrenaline caused an increase in the umbilical venous-arterial glucose difference at E15 and E17 with a concomitant increase in liver, brain and heart glycogen at E15. By E21 the response of liver glycogen to adrenaline was drastically reversed. Our data suggest that the mechanism regulating glucose homeostasis changes half way through fetal development. Tissue self-regulation is replaced with a centralized mechanism similar to that of the adult. This occurs just before birth as the liver becomes a reservoir for carbohydrates and responsive to insulin and adrenaline