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Elevated basal and post-feed glucagon-like peptide 1 (GLP-1) concentrations in the neonatal period
Raja Padidela1, Michael Patterson, Nawfal Sharief
1London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street, Hospital for Children NHS Trust, London, UK.
Insights
Neonates exhibit significantly higher levels of glucagon-like peptide 1 (GLP-1) after feeding compared to adults. These elevated GLP-1 concentrations may influence pancreatic development and enteroendocrine system maturation in newborns.
Area of Science:
- Endocrinology
- Neonatal Physiology
- Gastroenterology
Background:
- Glucagon-like peptide 1 (GLP-1) is a key incretin hormone regulating insulin secretion and beta-cell function.
- Adult GLP-1 levels range from 5-10 pmol/l fasting to ~50 pmol/l post-meal.
Purpose of the Study:
- To measure plasma glucose, insulin, and amidated GLP-1 in preterm and term neonates.
- To characterize the molecular forms of circulating GLP-1 in newborns.
Main Methods:
- Blood samples collected pre- and post-milk feed (20 and 60 min) from preterm (n=10) and term (n=12) infants.
- Reverse-phase fast protein liquid chromatography used for GLP-1 characterization.
Main Results:
- Mean basal GLP-1 was 79.1 pmol/l, rising to 156.6 pmol/l at 20 min and 121.5 pmol/l at 60 min post-feed.
- Over 75% of immunoreactivity was identified as GLP-1 (7-36) amide and (9-36) amide.
- Neonatal GLP-1 levels are substantially higher than adult levels.
Conclusions:
- Neonates show markedly elevated basal and post-feed amidated GLP-1 concentrations.
- High neonatal GLP-1 may play a role in enteroendocrine system maturation and pancreatic beta-cell development.
- Immature dipeptidyl peptidase IV activity or reduced glomerular filtration rate may contribute to elevated GLP-1 levels.
Background:
Glucagon-like peptide 1 (GLP-1) is an incretin hormone that stimulates glucose-induced insulin secretion, increases beta-cell proliferation, neogenesis and beta-cell mass. In adults, plasma concentrations of amidated GLP-1 are typically within the 5-10 pmol/l range in the fasting state and increases to approximately 50 pmol/l after ingestion of a mixed meal.
Research Design And Methods:
We measured plasma glucose, insulin and amidated forms of GLP-1 prefeed and then at 20 and 60 min post-feed following ingestion of a 60-70 ml of standard milk feed in preterm (n=10, 34-37 weeks) and term newborn infants (n=12, 37-42 weeks). Reverse-phase fast protein liquid chromatography was used to characterise the molecular nature of the circulating GLP-1.
Results:
Mean birth weight was 3.18 kg and mean age at sampling for GLP-1 was 7.7 days. The mean basal GLP-1 concentration was 79.1 pmol/l, which increased to 156.6 pmol/l (+/-70.9, P<0.001) and 121.5 pmol/l (+/-59.2) at 20 and 60 min respectively. Reverse-phase chromatography analysis suggested that the majority of GLP-1 immunoreactivity (>75%) represented GLP-1 (7-36) amide and (9-36) amide.
Conclusions:
Basal and post-feed amidated GLP-1 concentrations in neonates are grossly raised with the major fractions of circulating GLP-1 being (7-36) amide and (9-36) amide. Elevated GLP-1 concentrations in the newborn period may have a role in regulating maturation of enteroendocrine system and also of increasing pancreatic beta-cell mass and regeneration. The high levels of GLP-1 may be due to immaturity of the dipeptidyl peptidase IV and or lower glomerular filtration rate in the neonatal period. Further studies are required to understand the role of GLP-1 in the neonatal period.
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