In adults of several species including man, a small transient decrease in serum calcium concentration follows glucagon administration in doses of 1 to 10 mg/kg. The effects of maturation and insulin on this phenomenon were assessed by comparing the response of newborn and adult rats to equivalent doses of glucagon with and without prior insulin administration. After injection of 1 μg/g of glucagon, the decrease in serum calcium concentration at 60 min was significant in the newborn rats (-1.75 mg/dl; P < 0.001) and not significant in the intact adults (-0.07 mg/dl; P > 0.1).In pancreatomized adults, the decrease in serum calcium after the same dose of glucagon became significant (-1.23 mg/dl;P≤ 0.01). This hypocalcemic effect was prevented in the pancreatectomized adult rat if insulin in a dose of 0.01 μg was given 15 min before glucagon. In the newborn rats, the same dose of insulin decreased the hypocalcemic effect, but the change was still significant (-0.74 mg/dl;P≤ 0.01).Glucagon decreased serum calcium at one hr in newborn rats but not in adults. After pancreatectomy, the adult response to glucagon was significant and similar to that of the newborn. Insulin cancelled this effect of glucagon in the pancreatectomized adults and reduced it in the newborns.SpeculationHypocalcemia in the neonatal period is a common and probably multifactorial disorder. Glucagon is known to be a hypocalcemic agent; this effect is decreased by insulin. Because insulin secretion is sluggish in the neonatal period, glucagon may have a clinically significant effect on serum calcium concentration at this time.The frequency and severity of hypocalcemia within the first 48 hr of life are increased by prematurity, perinatal trauma, hypoxia, and maternal diabetes (3,10). Functional hypoparathyroidism has been demonstrated in some of these situations (3,10), but not all instances of hypocalcemia can be explained on this basis (3). Inasmuch as neonatal hypocalcemia is evidently a multifactorial disorder, all agents capable of affecting calcium homeostasis deserve consideration. Glucagon can lower serum calcium concentration in a variety of mammals including man (2, 6–9, 11), but no studies of this phenomenon in the neonatal period have been reported. Grajwerel al.(5) have pointed out that a large increase in immunoreactive plasma glucagon occurs within the first two hr after delivery. Because the newborn infant is particularly susceptible to disturbances of calcium homeostasis, we designed the following experiments to test the effects of maturation on the response of serum calcium concentration to exogenous glucagon.