Functional Ontogeny of the Proglucagon-Derived Peptide Axis in the Premature Human Neonate

Abstract

The regulation of intestinal growth and development in human neonates is incompletely understood, which hinders the provision of nutrients enterally. The "hindgut" hormones glucagon-like peptides 1 and 2 have been shown to play an important role in the regulation of nutrient assimilation, intestinal growth, and function. Our goal was to investigate the production of glucagon-like peptides 1 and 2 in premature human infants and examine the effects of prematurity and feeding on hormone release. With informed consent, premature infants who were admitted to a tertiary neonatal intensive care nursery (gestational age: 28-32 weeks) were monitored with weekly determinations of postprandial glucagon-like peptide 1 and 2 levels. Comparison studies with groups of normal infants and adults were performed. Hormone levels were obtained by using specific radioimmunoassay for glucagon-like peptide 1 (1-36) and glucagon-like peptide 2 (1-33), modified for small sample volumes; accurate monitoring of enteral intake was performed at all of the sampling time points. Forty-five infants with a mean gestational age of 29.6 +/- 1.9 weeks were studied; fasting levels of both glucagon-like peptides 1 and 2 were elevated. There was no correlation between gestational age and glucagon-like peptide 2 output. However, both glucagon-like peptide 1 and 2 levels were correlated with the caloric value of feeds. The premature human neonate has significantly higher fasting levels of glucagon-like peptides 1 and 2 compared with adults; feeding increases these levels further. These findings suggest that the proglucagon-derived peptides may have a role in normal intestinal development and nutrient handling.