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2 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada T6G 2P5; 3 The Research Institute, The Hospital for Sick Children, Toronto, Toronto, ON, Canada M5G 1X8; and Departments of 4 Paediatrics and 5 Nutritional Science, University of Toronto, Toronto, ON, Canada M5G 1X8
* To whom correspondence should be addressed. E-mail: ron.ball{at}ualberta.ca.
Parenterally fed neonatal piglets cannot synthesize sufficient arginine to maintain arginine status, presumably due to the intestinal atrophy that occurs with parenteral feeding. Parenteral feeding-induced atrophy can be reduced by the infusion of glucagon-like peptide 2 (GLP-2). GLP-2 infusion was hypothesized to increase the rate of endogenous arginine synthesis from proline, the major arginine precursor, in parenterally fed piglets receiving an arginine-deficient diet. Male piglets, fitted with jugular vein catheters for diet and isotope infusion, and femoral vein catheters for blood sampling (d 0), were allocated to a continuous infusion of either GLP-2 (n = 5; 10 nmol·kg1·d1) or saline (n = 5) for 7 d. Piglets received 2 d of a complete diet, followed by 5 d of an arginine-deficient [0.60 g·kg1·d1] diet. Piglets received primed, constant infusions of [guanido-14C]arginine to measure arginine flux (d 6) and [U-14C]proline (d 7) to measure proline conversion to arginine. Plasma arginine concentrations and arginine fluxes indicated a similar whole-body arginine status. Piglets receiving GLP-2 showed improvements in intestinal variables, including mucosal mass (P < 0.01) and villus height (P < 0.001), and a greater rate of arginine synthesis (µmol·kg1·h1) from proline (11.6 vs. 6.3) (P = 0.03). Mucosal mass (R2 = 0.71; P = 0.002) and villus height were correlated (R2 = 0.66; P = 0.004) with arginine synthesis. This study was the first to quantitate arginine synthesis in parenterally fed neonates and showed that although GLP-2 infusion increased arginine synthesis in a manner directly related to mucosal mass, this increased arginine synthesis was insufficient to improve whole-body arginine status in piglets receiving a low arginine diet.
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