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Title: GLUCAGON-LIKE PEPTIDE-2 ACUTELY INCREASES PROXIMAL SMALL INTESTINAL BLOOD FLOW IN TPN-FED NEONATAL PIGLETS.

Author
item STEPHENS, J - BAYLOR COLL OF MEDICINE
item STOLL, B - BAYLOR COLL OF MEDICINE
item COTTRELL, J - BAYLOR COLL OF MEDICINE
item CHANG, X - BAYLOR COLL OF MEDICINE
item HELMRATH, M - BAYLOR COLL OF MEDICINE
item Burrin, Douglas - Doug

Submitted to: American Journal of Physiology - Regulatory Integrative & Comparative Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2005
Publication Date: 12/1/2005
Citation: Stephens, J., Stoll, B., Cottrell, J., Chang, X., Helmrath, M., Burrin, D.G. 2006. Glucagon-like peptide-2 acutely increases proximal small intestinal blood flow in TPN-fed neonatal piglets. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 59:R283-R289.

Interpretive Summary: Premature infants usually are fed intravenously instead of orally for the first week of life because of an underdeveloped intestine. However, intravenous feeding or total parenteral nutrition (TPN) retards the normal growth and development of the newborn intestine, and can lead to serious diseases, like necrotizing enterocolitis. We have shown that a gut hormone secreted in response to oral feeding, called glucagon-like peptide 2 (GLP-2) is a potent growth factor for the neonatal intestine. Our studies in neonatal piglets also suggest the GLP-2 stimulates growth by increasing blood flow to the gut. The aim of the current study was to determine whether GLP-2 affects blood flow in different regions of the gut and if other body organs are also affected. We studied the rates of blood flow in various body organs in neonatal piglets given either TPN or TPN plus GLP-2 infusion for two hours. We found that the stimulation of blood flow in the gut occurs mainly in the upper region of the small intestine near the stomach and the pancreas, whereas blood flow in the stomach, large intestine, and kidney was slightly reduced. We also found that the stimulation of intestinal blood flow was relatively greater in the muscle layers than in the intestinal lining. Our results indicate that GLP-2 rapidly increases blood flow in the region of the intestine where the most growth occurs after GLP-2 treatment and is closely related to the amount of GLP-2 receptors.

Technical Abstract: GLP-2 is a gut hormone that is secreted in response to enteral feeding and stimulates small intestinal mucosal growth. We previously showed that GLP-2 infusion acutely increases portal venous blood flow in TPN-fed piglets. The aim of this study was to localize the vasoactive effect of GLP-2 within the gastrointestinal tissues and other visceral organs in TPN-fed piglets. Tissue blood flow rates were quantified using fluorescent microsphere deposition in anesthetized TPN-fed piglets given intravenous infusion of GLP-2 at either 500 pmol/kg**-1/hr**-1 (Low GLP-2, n = 7 pigs) or 2000 pmol/kg-1/hr**-1 (High GLP-2, n= 8 pigs) for 2 h. Compared to baseline, the low and the high GLP-2 treatment significantly increased the blood flow rate in the duodenum (+77%) and jejunum (+40% and 80%), respectively, but blood flow to the distal small intestine and colon (-15%) was unchanged or slightly decreased. Baseline mucosal blood flow was 5-fold higher than serosal blood flow; however, high GLP-2 treatment increased serosal (+140%) to a larger degree than mucosal blood flow (+73%). The high GLP-2 dose increased pancreatic flow (+34%), but decreased blood flow in the kidneys (-14%), stomach (-12%), whereas the spleen and brain was unaffected. These findings suggest that the acute GLP-2-mediated stimulation of portal blood flow in TPN-fed piglets occurs principally via increased blood flow through the superior mesenteric artery to the proximal small intestine, a tissue region where the GLP-2R mRNA abundance and trophic GLP-2 effects are greatest.