Bombesin Preserves the Exocrine Pancreas and Gut‐Islet Axis during Parenteral Nutrition

Abstract

Parenteral nutrition (PN) is the IV delivery of nutrients to individuals unable intake nutrients via the gut. During PN, intestinal and pancreatic physiology is compromised, leading to tissue atrophy and perturbed immune responses. In addition, PN is often associated with poor glucose control. We showed previously the gastrin releasing peptide analog, bombesin (BBS), enhanced gut immune response and architecture when administered during PN. Yet, the impact of BBS on pancreatic structure and function remained unclear. We hypothesized BBS treatment during PN would mitigate loss of exocrine pancreas structure and function and augment islet function. As compared to control mice, infusion of BBS during PN prevented exocrine tissue atrophy and preserved digestive enzyme secretion. Although there were no significant changes in gross islet morphology, we did observe increased β‐cell replication and function. We also found glucagon‐like peptide 1 (GLP‐1), a gut‐derived hormone with islet actions, was significantly elevated in plasma of mice BBS‐treated PN mice. Further, islets from BBS‐treated PN mice were significantly more responsive to a GLP‐1 receptor agonist. Finally, BBS increased intestinal cell proglucagon gene expression, suggesting it acts on the gut to promote GLP‐1 secretion in vivo. In sum, our data suggest that BBS preserves both exocrine and endocrine pancreas function during PN, with islet effects involving the gut‐pancreas axis.