Abstract
ObjectiveTo determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats.BackgroundGLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear.MethodsSprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition.ResultsResection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss.ConclusionsExogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.
Highlights
Neonatal short bowel syndrome (SBS) occurs after massive resection of the small bowel for various pathologies, including necrotizing enterocolitis, atresias and midgut volvulus
Resection increased the proportion of neuronal NOS (nNOS) immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by glucagon-like peptide-2 (GLP-2) therapy
The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study
Summary
Neonatal short bowel syndrome (SBS) occurs after massive resection of the small bowel for various pathologies, including necrotizing enterocolitis, atresias and midgut volvulus. SBS may lead to intestinal failure when there is inadequate bowel length necessary for survival, resulting in severe diarrhea, electrolyte abnormalities and failure to thrive. Initial management involves correction of electrolyte, acid base and fluid imbalances, along with nutritional support. Total parenteral nutrition (TPN) is used to provide calories until intestinal adaptation occurs. Intraluminal nutrients are potent stimuli for adaptation, triggering the release of enteric hormones such as glucagon-like peptide-2 (GLP-2) [3, 4]. GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). The effects of exogenous GLP-2 and SBS on enteric neurons are unclear
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