Submitted on June 7, 2007
Accepted on September 19, 2007
GLUCAGON-LIKE PEPTIDE 2 HAS LIMITED EFFICACY
TO INCREASE NUTRIENT ABSORPTION IN FETAL AND PRETERM PIGS
Per T Sangild1, Christiane Malo2, Mette Schmidt3, Yvette M Petersen1, Jan Elnif4, Jens Juul Holst5, and Randal K Buddington6*
1 Human Nutrition, University of Copenhagen, Frederiksberg C, Denmark
2 Physiology, University of Montreal, Montreal, Canada
3 Nutrition and Reproduction, University of Copenhagen, Denmark
4 Nutrition and Reproduction, University of Copenhagen, Frederiksberg C, Denmark
5 Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen,, Denmark
6 Health and Sports Sciences, University of Memphis, Memphis, Tennessee, United States
* To whom correspondence should be addressed. E-mail: rbddngtn{at}memphis.edu.
Exogenous glucagon-like peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis that the immature intestine of fetuses and preterm neonates has a diminished nutrient absorption response to exogenous GLP-2. This was accomplished using catheterized fetal pigs infused for 6 d (87-91% of gestation) with GLP-2 (25 nmol kg-1 d-1, i.v., n = 7) or saline (n = 7), and caesarean-delivered preterm pigs (92% of gestation) that received TPN with GLP-2 (25 nmol kg-1 d-1, i.v, n = 8) or saline (n = 7) for 6 d after birth. Responses to GLP-2 were assessed by measuring intestinal dimensions, absorption of nutrients (glucose, leucine, lysine, proline) by intact tissues and brush border membrane vesicles (BBMV), and abundance of sodium-glucose cotransporter, (SGLT-1) mRNA. Infusion of GLP-2 increased circulating GLP-2 levels in fetuses, but did not increase intestinal mass or absorption of nutrients by intact tissues and BBMV, except for lysine. Administration of exogenous GLP-2 to preterm TPN-fed pigs similarly did not increase rates of nutrient absorption, yet nutrient absorption capacities of the entire small intestine tended to increase (+10-20%, P < 0.10) compared with TPN alone due to increased intestinal mass (+30%, P < 0.05). GLP-2 infusion did not increase SGLT-1 mRNA abundance in fetuses or postnatal preterm pigs. Hence, the efficacy of exogenous GLP-2 to improve nutrient absorption by the intestine of fetal and preterm pigs is limited compared with term pigs and more mature animals and humans.
