SUN-541 An Immunofluorescence Study of the Effect of Parenteral Nutrition on the Development of the Porcine Endocrine Pancreas

Abstract Disclosure: A.N. Nagarapu: None. S. Mehta: None. A. Sims: None. K. Kurashima: None. C. Manithody: None. M. Swiderska-Syn: None. A.K. Jain: None. Introduction: Short Bowel Syndrome (SBS) is a rare condition characterized by significantly reduced functional bowel as a sequelae of major pediatric illnesses such as necrotizing enterocolitis, which require resection of nonfunctional intestine. Many such patients depend on total parenteral nutrition (TPN) for adequate nutrition in the absence of enteral feeding, but the high dextrose content of TPN has been associated with hyperinsulinemia. The importance of native gut microbiota has also been examined for its effects on glucose metabolism. We have previously explored the effects of SBS and TPN and its effects on enteral signaling in our novel SBS piglet models. Here, we conducted a secondary analysis on the pancreata of piglets from these studies. Methods: Piglets aged 7-10 days were separated into groups that received enteral milk feeds for 14-15 days (Milk, n = 3), received 75% small bowel resection with ilio-colonic anastomosis followed by TPN for 11 days (SBS-TPN, n = 3), or received bowel resection, TPN, and Poly-Prebiotic powder (Pure Encapsulations, Sadbury, MA) (SBS-Pre Biotic, n = 2). Samples of pancreata were snap frozen, cryosectioned and stained for insulin (Ins+), glucagon (Gluc+), and chromogranin A (CgA+). Five random 20x images were collected and analyzed for ICC area and cell composition using QuPath (QuPath-0.5.0-arm64). An ICC was determined by a dual positive stain of CgA and one of the two hormonal stains on a region greater than 50 µm2. Results: The number of ICCs exponentially decreased with increasing size among all groups. ICC area ranged from 61 - 27821 µm2 with varying degrees of circularity. The average number of glucagon dominant cells, average proportion glucagon positive, and average proportion insulin positive were significantly different between groups (One-Way ANOVA with unequal variance, p = 0.040, p =0.021, p = 0.049, respectively). In the range of 4001-5000 µm2, the Milk group had a greater proportion of Ins+ cells than SBS-TPN (Ins+ 40.59 ± 9.02% vs. 6.12 ± 0.00%, p adjusted = 0.29). In the SBS-TPN treated animals, ICCs in the range of 1001-2000 µm2 had a lower proportion of Gluc+ cells per ICC than those in the range of 2001-3000 µm2 (Gluc+ 21.15 ± 4.07% vs. 39.44 ± 0.79%, p adjusted = 0.013) and greater proportion Ins+ cells (Ins+ 63.01 ± 5.02% vs. 45.42 ± 1.77%, p adjusted = 0.016). Conclusions: These results may offer insight in the development of the endocrine pancreas in neonatal piglets with SBS that receive TPN over enteral feeds in normal animals. Further studies may delineate the individual effects of TPN and bowel resection, including evaluation of glucose tolerance in these animals and ex vivo analysis of the isolated ICCs over the course of the treatment. Presentation: Sunday, July 13, 2025