Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

Abstract

Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are essential for maximal resection-induced intestinal growth. Rats received systemic or perivagal capsaicin or ganglionectomy before 70% midjejunoileal resection or transection and were fed orally or by total parenteral nutrition (TPN) for 7 days after surgery. Growth of residual bowel was assessed by changes in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle. Sucrase specific activity in jejunal mucosa was not significantly different; ileal mucosal sucrase specific activity was significantly increased by resection in capsaicin-treated rats. Capsaicin did not alter the 57% increase in ileal proglucagon mRNA or the 150% increase in plasma concentration of bioactive GLP-2 resulting from resection in orally fed rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not attenuate resection-induced mucosal growth. We conclude that vagal afferents are not essential for GLP-2 secretion when the ileum has direct contact with luminal nutrients after resection. In summary, vagal afferent neurons are essential for maximal resection-induced intestinal adaptation through a mechanism that appears to involve stimulation by luminal nutrients.

Exogenous Glucagon‐Like Peptide‐2 (GLP‐2) Augments GLP‐2 Receptor mRNA and Maintains Proglucagon mRNA Levels in Resected Rats

“…33 Indeed our study confirmed increased expression of proglucagon mRNA in ileum following resection. One aim of this study was to assess whether exogenous GLP-2 down-regulates endogenous proglucagon expression.…”

Temporal Changes in the Intestinal Growth Promoting Effects of Glucagon-Like Peptide 2 Following Intestinal Resection

“…Control animals did not undergo a transection, so that the effects of GLP-2 on intact bowel could be compared with the effects on resected bowel. This methodology dose not allow for an assessment of the effects of transection alone; transection has been shown to alter motility, neuronal, and potentially adaptation in previous studies, and so is important physiologically, but would not be done in isolation clinically [17]. Animals were followed until d 3 or 10 postsurgery, and further divided into groups receiving GLP-2 (10 g/kg given i.p.)…”

Duodenal Disaccharidase Activities During and After Weaning off Parenteral Nutrition in Pediatric Intestinal Failure

“…Following intestinal resection, the remaining intestine efforts to compensate the loss off functional intestinal surface by adaptive changes (2,(14)(15)(16)(17). In animal models, enteral nutrition stimulates brush-border enzyme activities, including maltase and sucrase, villus height, crypt depth, cell proliferation, and reduces apoptosis (15,(17)(18)(19)(20).…”

“…Following intestinal resection, the remaining intestine efforts to compensate the loss off functional intestinal surface by adaptive changes (2,(14)(15)(16)(17). In animal models, enteral nutrition stimulates brush-border enzyme activities, including maltase and sucrase, villus height, crypt depth, cell proliferation, and reduces apoptosis (15,(17)(18)(19)(20). PN is a lifesaving treatment when enteral absorption is insufficient to provide nutritional requirements (21), but in combination with enteral nutrient deprivation it predisposes to mucosal atrophy, loss of intestinal barrier function, and IF-associated liver disease (3,5,(22)(23)(24)(25)(26).…”

“…Important predictors of enteral autonomy in children with IF include length of the remaining small bowel and colon, presence of the ileocecal valve, and the absence of enterostomy (28)(29)(30)(31). Intestinal adaptation is regulated by enterohormones, including glucagon-like peptide-2 (GLP-2), secreted from ileal and colonic L-cells (17,32). In animal models and in humans, GLP-2 has been shown to act as an enterotrophic agent and to enhance intestinal nutrient and fluid absorption and to improve intestinal adaptation (33)(34)(35)(36)(37).…”