The effect of intravenous glucagon on plasma amino acids in the newborn

Abstract

The relationship between glucagon stimulation at a pharmacologic dose level (300 μg/kg) and amino acids in systemic venous plasma was examined in four groups of newborn infants. Full term infants (FT), (mean age, 12.5 hr), infants of diabetic mothers (IDM), (mean age, 3.33 hr), infants who were small for gestational age (SGA), (mean age, 7.5 hr), were studied on the day of birth either before, or 4 hr after the first feeding; FT infants were studied on the 3rd day of life (mean age, 80 hr), 4 hr after feeding. The mean total amino acid concentration in venous plasma on the day of birth is 2,999 ± 147 μmol/liter in FT infants, 2,952 ± 536 / μmol/liter in IDM infants, and 1,867 ± 320 μmol/liter in the SGA group (P < 0.005 compared with FT group). Since plasma amino acid levels normally fall rapidly, the level in the IDM group is lower than expected for the postnatal age of this group on the day of birth. Several amino acids, notably, glutamine plus asparagine, and glycine contribute to the very low total amino acid level in SGA infants. Total amino acid concentration in FT infants falls to 2,444 =1= 395 μmol/liter by the 3rd day of life. Two important glucogenic amino acids, glycine and alanine, account for half of the net decline, whereas the branched chain amino acids show a net rise in plasma by the 3rd day. Glucagon infusion produces a hypoaminoacidemic response at 30 min on the 3rd day of life, a reaction which resembles that of the adult. Glutamine plus asparagine (absolute change (Δ), −165 μmol/liter), glycine (Δ, −55 μmol/liter), alanine (Δ, −45 /μmol/liter), and proline (Δ, −40 / μmnol/liter), the amino acids with the most important gluconeogenic functions in liver and kidney, account for about 60% of the total net decline in the total plasma amino acid level. The response to glucagon is attenuated on the day of birth in the FT infant. The IDM group is insensitive to glucagon, whereas the response in the SGA group mimics FT infants. Blood glucose on the day of birth is depressed in IDM (20.2 ± 4.4 mg/100 ml) and SGA (28.6 ± 3.5 mg/100 ml) infants compared with full term infants (45 ± 4.7 mg/100 ml). Basal serum insulin on the day of birth is elevated fivefold above FT values (2.0 ± 0.77 / μml) in IDM and SGA groups. All groups have an insulinemic response to glucagon (Δ, > + 23 μU/ml) and the peak insulin response is highest in the SGA group. The basal level of serum growth hormone is elevated in the SGA group on the day of birth (51.9 ± 15.6 ng/ μml) compared with full term infants (15.1 ± 4.1 ng/ μml). All groups show a growth hormone (HGH) response to glucagon. Speculation: On the day of birth, mechanisms which protect the fetus from hypoglycemia in utero (maternal glucose supply and high growth hormone levels) are withdrawn, and splanchnic glucogenic mechanisms should become activated. The apparent inability of the neonate to extract the important gluconeogenic amino acids, alanine and proline, from plasma after a glucagon stimulus on the 1 st day of life may account for the susceptibility to hypoglycemia after birth when added stresses exist, as in the infant who is small for gestational age or born to a diabetic mother. © 1973 International Pediatric Research Foundation, Inc.