Glucagon-like peptide-2 protects against TPN-induced intestinal hexose malabsorption in enterally refed piglets

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, duodenum, and a portal vein flow probe in piglets before providing either enteral formula (ENT), TPN or a coinfusion of TPN plus GLP-2 for 6 days. On postoperative day 7, all piglets were fed enterally and digestive functions were evaluated in vivo using dual infusion of enteral ((13)C) and intravenous ((2)H) 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 with 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 with ENT pigs. The enhanced hexose absorption in GLP-2 compared with 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 [(13)C]glucose to [(13)C]lactate. Our findings indicate that GLP-2 treatment during chronic TPN maintains intestinal structure and lactose digestive and hexose absorptive capacities, reduces intestinal hexose metabolism, and may facilitate the transition to enteral feeding in TPN-fed infants.

Transport of nutrients and electrolytes across the intestinal wall in pigs

“…GLUT2 (protein level) and GLUT5 (mRNA level) have also been detected in the small intestine of pigs by Cottrell et al (2006) and Xiao et al (2004), respectively. Interestingly, as in rats GLUT2 abundance could be demonstrated in the intestinal brush-border membrane of pigs, but the functional properties and relevance for overall sugar absorption have still to be examined.…”

GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets

“…Our previous piglet studies demonstrated that chronic treatment (7 days) with therapeutic doses of GLP-2 prevents the mucosal atrophy associated with TPN, and this translates into improved intestinal function (4,5,10). Recent studies show that GLP-2 rapidly activates small intestinal blood flow, whereas the transition from enteral to parenteral nutrition leads to reduced intestinal blood flow, which precedes the onset of mucosal atrophy (14, 29, 40).…”

Disruption of the Murine Glp2r Impairs Paneth Cell Function and Increases Susceptibility to Small Bowel Enteritis

“…GLP-2 also increases intestinal blood flow (3,4) and gut barrier function (5) and enhances nutrient absorption via stimulation of glucose transport activity (6,7). Moreover, GLP-2 infusion enhances lipid absorption and chylomicron secretion in mice (8) and increases postprandial levels of triglycerides and free fatty acids in normal human subjects (9).…”