Glucagon‐Like Peptide 2 Stimulates Postresection Intestinal Adaptation in Preterm Pigs by Affecting Proteins Related to Protein,Carbohydrate, and Sulphur Metabolism

Background: Exogenous glucagon‐like peptide 2 (GLP‐2) stimulates intestinal adaptation after resection in animal models of pediatric short bowel syndrome (SBS). It is unknown whether the molecular mechanisms of such GLP‐2 effects are similar to those of postresection spontaneous adaptation. Using preterm pigs as a model, we hypothesized that GLP‐2 treatment would change the intestinal proteome within the first week after resection, relative to individuals not resected or resected without GLP‐2 treatment. Materials and Methods: Two‐day‐old preterm pigs were subjected to resection of 50% distal small intestine and fed total parenteral nutrition without (SBS) or with GLP‐2 infusion (3.5 µg/kg/h, SBS+GLP‐2) for 5 days. The proteome of the remnant proximal intestine was compared among the SBS, SBS+GLP‐2, and unresected pigs, through gel‐based proteomics. Results: Thirty‐two proteins with differential expression were identified. Ten of these proteins were affected by the resection alone (ie, SBS vs unresected pigs). Five of these resection‐responsive proteins and another 22 proteins were affected by GLP‐2 infusion (ie, SBS+GLP‐2 vs SBS or unresected pigs). Resection alone mainly affected cellular structural proteins, while the added GLP‐2 treatment affected proteins involved in protein processing and the metabolism of protein, carbohydrate, and sulphur. Conclusion: In the first days following resection, proteins affected by resection plus GLP‐2 treatment differed markedly from those affected by the spontaneous intestinal adaptation following resection alone. Whether more long‐term GLP‐2 treatment may affect the intestinal proteome following intestinal resection remains unknown.