GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1.
OBJECTIVE
Our aim was to determine whether the intestinotrophic effects of GLP-2 are mediated by acute up-regulation of intestinal substrate utilization in TPN-fed piglets.


METHODS
Twenty-four 12-day-old pigs, fitted with a portal flow probe and carotid, jugular and portal catheters, were fed by TPN for 7 days. On day 8, a group of pigs (n = 8) was infused intravenously with saline (control) for 4 hours and then with GLP-2 (500 pmol x kg(-1) x hour(-1), GLP-2) for 4 hours. (2)H-glucose and (13)C-phenylalanine were infused to estimate their kinetics and protein turnover. Another group (n = 8) received consecutive intravenous infusions of saline, GLP-2, and GLP-2 plus N(G)-Nitro-L-arginine methyl ester (L-NAME, 50 micromol x kg(-1) x hour(-1)) for 4 hours each.


RESULTS
GLP-2 acutely increased portal-drained visceral (PDV) blood flow rate (+25%) and intestinal blood volume (+51%) in TPN-fed piglets. GLP-2 also increased intestinal constitutive nitric oxide synthase (NOS) activity and endothelial NOS protein abundance. GLP-2 acutely increased PDV glucose uptake (+90%) and net lactate production (+79%). Co-infusion of GLP-2 plus L-NAME did not increase either PDV blood flow rate or glucose uptake. GLP-2 increased PDV indispensable amino acid uptake by 220% and protein synthesis by 125%, but did not decrease protein breakdown or phenylalanine oxidation.


CONCLUSIONS
We conclude that in TPN-fed neonatal pigs, GLP-2 acutely stimulates intestinal blood flow and glucose utilization, and this response is nitric oxide-dependent. These findings suggest that GLP-2 may play an important physiological role in the regulation of intestinal blood flow and that nitric oxide is involved in GLP-2 receptor function.
Guan
Xinfu
X
USDA/ARS Children's Nutrititin Research Center, Department of Pediatircs, Baylor College of Medicine, Houston, Texas 77030, USA.
Stoll
Barbara
B
Lu
Xiaofeng
X
Tappenden
Kelly A
KA
Holst
Jens J
JJ
Hartmann
Bolette
B
Burrin
Douglas G
DG
D000596:Amino Acids / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D004044:Dietary Proteins / Q000493:pharmacokinetics; D005260:Female; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000493:pharmacokinetics*; D007422:Intestines / Q000098:blood supply*; D008102:Liver Circulation; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010101:Oxygen Consumption; D010187:Pancreatic Hormones / Q000097:blood / Q000494:pharmacology; D010289:Parenteral Nutrition, Total; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D011168:Portal System / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D034421:Sus scrofa; D015854:Up-Regulation
D000596:Amino Acids; D004044:Dietary Proteins; D053767:Glucagon-Like Peptide 2; D010187:Pancreatic Hormones; D010455:Peptides; D009569:Nitric Oxide; D004763:Glucagon-Like Peptides; D019001:Nitric Oxide Synthase; D005947:Glucose