glucagon-like-peptide-2 and Ischemia

Glucagon-like peptide-2 (GLP-2) is a 33-amino-acid proglucagon-derived peptide secreted from enteroendocrine L cells. GLP-2 circulates at low basal levels in the fasting period, and plasma levels rise rapidly after food ingestion. Renal clearance and enzymatic inactivation control the elimination of bioactive GLP-2. GLP-2 increases mesenteric blood flow and activates proabsorptive pathways in the gut, facilitating nutrient absorption. GLP-2 also enhances gut barrier function and induces proliferative and cytoprotective pathways in the small bowel. The actions of GLP-2 are transduced via a single G protein-coupled receptor (GLP-2R), expressed predominantly within the gastrointestinal tract. Disruption of GLP-2R signaling increases susceptibility to gut injury and impairs the adaptive mucosal response to refeeding. Sustained augmentation of GLP-2R signaling reduces the requirement for parenteral nutrition in human subjects with short-bowel syndrome. Hence GLP-2 integrates nutrient-derived signals to optimize mucosal integrity and energy absorption.

Topics: Animals; Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Tract; Glucagon-Like Peptide 2; Glucagon-Like Peptide-2 Receptor; Humans; Intestinal Absorption; Ischemia; Radiation Injuries; Receptors, Glucagon; Short Bowel Syndrome; Signal Transduction

A major objective of necrotizing enterocolitis (NEC) research is to devise a noninvasive method of early detection. We hypothesized that abdominal near-infrared spectroscopy (A-NIRS) readings will identify impending NEC in a large animal model.. Piglets were prematurely delivered and received parenteral nutrition followed by enteral feedings. Serial A-NIRS readings were obtained for 5 days, and animals were monitored for NEC. Separately, A-NIRS readings were obtained in healthy piglets to validate the correlation of A-NIRS with splanchnic oxygen delivery.. Of 29 piglets, 3 developed NEC. Eleven piglets without NEC died prematurely. Fifteen piglets remained healthy, had normal histologic assessment of their intestines, and served as controls. Abdominal near-infrared spectroscopy readings within 12 hours of birth were significantly lower in animals that developed NEC compared with healthy littermates (4% vs 33%, P = .02). For all time-points measured, A-NIRS readings were significantly lower in the NEC group compared with controls (21% vs 55%, P < .001). Abdominal near-infrared spectroscopy readings correlated with both decreased pulse oximetry readings during apneic episodes (r = 0.96) and increased superior mesenteric artery flow in response to glucagon-like peptide 2 (r = 0.67).. Abdominal near-infrared spectroscopy is capable of detecting alterations in intestinal oxygenation and perfusion in neonatal piglets and may allow early detection of neonates at risk for NEC.

Topics: Analysis of Variance; Animals; Animals, Newborn; Biopsy, Needle; Blood Flow Velocity; Disease Models, Animal; Enterocolitis, Necrotizing; Female; Glucagon-Like Peptide 2; Humans; Immunohistochemistry; Infant, Newborn; Infant, Premature, Diseases; Infusions, Intravenous; Intestines; Ischemia; Mesentery; Oxygen; Oxygen Consumption; Pregnancy; Random Allocation; Reference Values; Spectroscopy, Near-Infrared; Swine