Title: GLUCAGON-LIKE PEPTIDE-2 PROTECTS AGAINST TPN-INDUCED INTESTINAL HEXOSE MALABSORPTION IN ENTERALLY RE-FED PIGLETS. Authors
|Cottrell, J - BAYLOR COLLEGE MED|
|Stoll, B - BAYLOR COLLEGE MED|
|Buddington, R - MISSISSIPPI STATE UNIV.|
|Stephens, J - BAYLOR COLLEGE MED|
|Cui, L - BAYLOR COLLEGE MED|
|Chang, X - BAYLOR COLLEGE MED|
Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 1, 2005
Publication Date: December 1, 2005
Citation: Cottrell, J.J., Stoll, B., Buddington, R.K., Stephens, J.E., Cui, L., Chang, X., Burrin, D.G. 2005. Glucagon-like peptide-2 protects against TPN-induced intestinal hexose malabsorption in enterally re-fed piglets. American Journal of Physiology - Gastrointestinal and Liver Physiology. 53:G293-G300. Interpretive Summary: Premature infants are unable to consume food normally when then are born because of an underdeveloped intestine. Thus, premature infants usually are fed intravenously for the first week of life in order to obtain nourishment. A problem with intravenous feeding, also called total parenteral nutrition or TPN, is that it retards the normal growth and development of the newborn intestine. Poor intestinal development in premature infants 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. We have also shown that infusing GLP-2 intravenously can stimulate intestinal growth in neonatal piglets even when they are fed by TPN. The aim of the current study was to determine whether the stimulation of intestinal growth associated with GLP-2 treatment would translate into better intestinal function, especially the digestion and absorption of milk sugars. We studied neonatal piglets given either TPN or TPN plus GLP-2 treatment for six days. After six days, we fed both groups normally via the oral route and measured the rate of lactose digestion and glucose absorption. Our results showed that TPN significantly impairs both lactose digestion and glucose absorption. However, TPN-fed piglets treated with GLP-2 had better rates of lactose digestion and glucose absorption. Our results also indicate that the improved intestinal function in GLP-2-treated piglets resulted from the stimulation in intestinal lining and increased activity of intestinal cells to transport glucose into the blood. These studies suggest that treating TPN-fed premature infants with GLP-2 could be a therapy to improve digestive function and prevent the incidence of intestinal disease.
Technical Abstract: 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.