GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1

Gastroenterology. 2003 Jul;125(1):136-47. doi: 10.1016/s0016-5085(03)00667-x.


Background & aims: 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / pharmacokinetics
  • Animals
  • Animals, Newborn
  • Dietary Proteins / pharmacokinetics
  • Female
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptides
  • Glucose / pharmacokinetics*
  • Intestines / blood supply*
  • Liver Circulation
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Oxygen Consumption
  • Pancreatic Hormones / blood
  • Pancreatic Hormones / pharmacology
  • Parenteral Nutrition, Total*
  • Peptides / blood
  • Peptides / pharmacology*
  • Portal System / drug effects
  • Regional Blood Flow / drug effects
  • Sus scrofa
  • Up-Regulation


  • Amino Acids
  • Dietary Proteins
  • Glucagon-Like Peptide 2
  • Pancreatic Hormones
  • Peptides
  • Nitric Oxide
  • Glucagon-Like Peptides
  • Nitric Oxide Synthase
  • Glucose