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Am J Physiol Gastrointest Liver Physiol (September 15, 2005). doi:10.1152/ajpgi.00275.2005
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Submitted on June 15, 2005
Accepted on September 13, 2005

Glucagon-Like Peptide-2 Protects Against TPN-induced Intestinal Hexose Malabsorption in Enterally Re-fed Piglets

J. J. Cottrell1, B. Stoll1, R. K. Buddington2, J. E. Stephens1, L. Cui1, X. Chang1, and D. G. Burrin1*

1 Department of Pediatrics, Baylor College of Medicine, USDA-ARS, Children's Nutrition Research Center, Houston, TX, USA
2 Department of Biological Sciences, Mississippi State University, Starkville, MS, USA

* To whom correspondence should be addressed. E-mail: dburrin{at}bcm.tmc.edu.

Premature infants receiving chronic total parenteral nutrition (TPN) due to feeding intolerance develop intestinal atrophy and reduced nutrient absorption. Although providing the intestinal trophic hormone glucagon-like peptide 2 (GLP-2) during chronic TPN improves intestinal growth and morphology, it is uncertain whether GLP-2 enhances absorptive function. We placed catheters in the carotid artery, jugular and portal veins, and duodenum, and a portal vein flow probe in piglets before providing either enteral formula (ENT), TPN or a co-infusion of TPN plus GLP-2 for 6 days (d). On the 7th post-operative day all piglets were fed enterally and digestive functions were evaluated in vivo using dual infusion of enteral (13C) and intravenous (2H) glucose, in vitro by measuring mucosal lactase activity and rates of apical glucose transport, and by assessing the abundances of sodium glucose transporter-1 (SGLT-1) and glucose transporter-2 (GLUT2). Both ENT and GLP-2 pigs had larger intestine weights, longer villi and higher lactose digestive capacity and in vivo net glucose and galactose absorption compared to TPN alone. These endpoints were similar in ENT and GLP-2 pigs, except for a lower intestinal weight and net glucose absorption in GLP-2 compared to ENT pigs. The enhanced hexose absorption in GLP-2 compared to TPN pigs corresponded with higher lactose digestive and apical glucose transport capacities, increased abundance of SGLT-1, but not GLUT-2, and lower intestinal metabolism of 13C-glucose to 13C-lactate. Our findings indicate that GLP-2 treatment during chronic TPN maintains intestinal structure, lactose digestive and hexose absorptive capacities, reduces intestinal hexose metabolism, and may facilitate the transition to enteral feeding in TPN fed infants.




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