|Burrin, Douglas - Doug|
Submitted to: Gastroenterology
Publication Type: Abstract only
Publication Acceptance Date: 3/1/2005
Publication Date: 4/1/2005
Citation: Bartholome, A.L., Stoll, B., Burrin, D.G., Tappenden, K.A. 2005. Glucagon-like peptide-2 increases glucose uptake by increasing Sglt-1 and Glut2 abundance in tpn-fed neonatal pigs [abstract]. Gastroenterology. 128:A677. Interpretive Summary:
Technical Abstract: Children with intestinal dysfunction, often require total parenteral nutrition (TPN) to meet their nutritional needs. Although TPN provides the necessary nutrition, it may limit intestinal adaptation, growth, and restoration of normal function. The trophic gut peptide, glucagon-like peptide-2 (GLP-2), which has been shown to reduce TPN associated atrophy and increase glucose uptake, may also enhance intestinal function. Therefore, we examined the effects of GLP-2 on the protein abundance of the brush border sodium-dependent glucose transporter, SGLT-1, and the basolateral sodium-independent glucose transporter, GLUT2. Thirty-two neonatal piglets were randomized to one of five diets for seven days: 1) enterally administered sow milk replacer (EN; n=6); 2) TPN+saline (TPN; n=9); 3) TPN+GLP-2 (3.125 nmol/kg BW; Low; n=5); 4) TPN+GLP-2 (6.25 nmol/kg BW; Med; n=5); and 5) TPN+GLP-2 (12.5 nmol/kg BW; High; n=7). The protein abundance of the apical sodium-dependent glucose transporter (SGLT-1) and the basolateral glucose transporter (GLUT2) were measured by Western blotting in the proximal jejunum, distal jejunum, proximal ileum and distal ileum. The SGLT-1 protein abundance in the EN group (P<0.0001) was significantly higher than all TPN groups. There was a trend for the High-GLP-2 dose to increase SGLT-1 to enteral levels. The effect was most marked in the distal small intestine. In contrast, the Low-GLP-2 dose significantly (P=0.025) increased GLUT2, particularly in the proximal region. These data suggest that TPN decreases SGLT-1 protein abundance below that of enteral levels. This can be partially reversed by a High-GLP-2 dose. In contrast, the protein abundance of GLUT2 was not lowered by TPN but was upregulated especially at the Low-, most physiologically relevant, GLP-2 dose used. Therefore, the addition of GLP-2 to TPN formulations may enhance intestinal function and decrease the period of TPN dependence of children with intestinal dysfunction.