Functional enteroinsular axis in full-term newborn infants.

The term "enteroinsular axis" refers to the AGA, appropriate for gestational age enhancement of insulin release by hormones secreted from SGA, small for gestational age the gut. Gastric inhibitory polypeptide (GIP) is one of the LGA, large for gestational age major hormones that mediates this function. The purpose IDM, infant of diabetic mother of the present study was to examine whether the enteroin- IRI, immunoreactive insulin sular axis is functional in newborn infants born at term gestation. Between d 2 and d 4 of life, glucose was infused for 2 h intravenously or orogastrically to 44 fullterm new- born infants, of whom 18 were appropriate for gestational age, nine large for gestational age, eight small for gesta- tional age; nine infants were born to diabetic mothers. Glucose was infused at either 8 mg/kg/min intravenously or 16 mg/kg/min orogastrically to achieve similar plasma glucose concentrations. Plasma insulin and GIP concentra- tions were compared. Plasma GIP concentration increased significantly with enteral glucose administration in all in- fants but remained unchanged with parenteral glucose in- fusion. The responses of plasma insulin and the insulin/ glucose ratio were significantly greater in infants receiving enterally than parenterally infused glucose. However, when glucose was infused orogastrically at a lower rate (8 mg/ kg/min), plasma GIP concentrations rose, but no enhance- ment of insulin response was detected, suggesting the importance of the role of circulating glucose in the "enter- oinsular axis". The infants of diabetic mothers and the large-for-gestational-age infants had more rapid insulin response to orogastrically administered glucose, but their GIP responses were similar to that of normal infants. These findings suggest that, at term gestation, the newborn in- fants have a "functional" enteroinsular axis in response to glucose, i.e. the rising plasma GIP contributed in part to the enhanced insulin response to enterally infused glucose. However, the more rapid insulin response to enteral glu- cose in the infant of diabetic mothers probably results from the effect of intrauterine hyperglycemia. Our data could not separate the role of GIP in insulin response to enteral glucose in the infants of diabetic mothers. (Pediatr Res 25:490-495, 1989) During the transition from fetal to neonatal life, the newborn infant initiates nutrient assimilation by the enteral route for the first time. The fetus in utero acquires its nutrients primarily via the transplacental route. Although amniotic fluid contains small amounts of nutrients such as glucose, amino acids, and ketone bodies, and the fetus swallows amniotic fluid continuously, the nutrient contribution of amniotic fluid to fetal growth is assumed to be negligible. In addition, the effect of in utero nutrient intake on gastrointestinal hormonal responses is not known. In adults, an enhanced insulin release occurs when glucose is administered enterally as compared to glucose given parenterally (1). The term "enteroinsular axis" was first used by Unger (2) in 1969 to describe this enhanced insulin response. The peptide hormone GIP has been shown to be one of the major hormones that mediates the gastrointestinally enhanced insulin release (3, 4). In recent years, postnatal surges of several gastrointestinal hormones have been described in both term and preterm new- born infants (5, 6). The functional capacity of the enteroinsular axis and its contribution to nutrient assimilation, however, have not been defined. Lucas et al. have examined the developmental aspects of GIP secretion and its possible role in the enteroinsular axis in neonates (7-10). They have demonstrated an increase in basal GIP concentrations by age 6 d postnatally, in both term and preterm infants who received enteral feeding. However, the associated postprandial response of GIP and insulin with feedings was not clear-cut. We have previously demonstrated a lack of enhanced insulin rise when small dose of glucose was adminis- tered orally (1 I), but enhancement of insulin release by enteral glucose was demonstrated with adequate glucose stimulus (12). The present studv was designed to examine whether the "en- teroinsilar" axis is iunctionayat birth by comparing the plasma Abbreviations insulin and GIP responses to enterally or parenterally adminis-