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Gut growth and glucose tolerance in newborn pigs subjected to prenatal protein restriction and postnatal Glucagon-like Peptides
Authors:PT Sangild  MH Schmidt  T Thymann  JJ Holst  K Raun
Institution:

aHuman Nutrition, Faculty of Life Sciences, University of Copenhagen, 30 Rolighedsvej, DK-1958 Frederiksberg C

bNOVO Nordisk, NOVO Allé, DK-2880 Bagsværd, Denmark

cPanum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark

Abstract:Fetal protein restriction is potentially associated with organ dysfunctions after birth (e.g. impaired gut growth, glucose tolerance and pancreatic β-cell function). Just after birth, gut growth and maturation is stimulated by enteral food intake, and inhibited by total parenteral nutrition (TPN), in part mediated via differential release of insulino- and intestino-tropic hormones like the Glucagon-Like Peptides 1 and 2 (GLP-1, GLP-2). We hypothesized that short-term co-infusion of GLP-1 and GLP-2 would stimulate pancreatic and intestinal growth in newborn TPN-fed pigs subjected to prenatal protein restriction. Two sows were fed a protein-restricted diet (PR: 8% crude protein during last 50% of gestation) while a third sow was fed a control diet (C: 15% crude protein). PR pigs were killed either at birth (n = 7) or after 3 days TPN with (n = 6) or without (n = 4) intravenous infusion of a mixture of synthetic human GLP-17–37 and GLP-21–33 (each 50 μg/kg/d). At birth, PR piglets did not show reduced body weight, relative to controls (1.45 vs. 1.50 kg), but significantly reduced weight of the small intestine (18.0 ± 0.6 vs. 21.9 ± 0.5 g/kg, P < 0.001) and a marginally reduced pancreas weight (0.85 ± 0.02 vs. 0.93 ± 0.04 g/kg, P = 0.10). Co-infusion GLP-1 and GLP-2 into PR pigs resulted in increased basal glucose levels (5.3 vs. 4.0 mM), and glucose-stimulated insulin release, but did not have any significant effect on body weight, or weight of internal organs (heart, lungs, spleen, kidneys, adrenals, stomach, colon, liver, intestine, pancreas). We conclude that short-term (3 days) infusion of native GLP-1 and GLP-2 does not stimulate gut growth or glucose tolerance in TPN-fed piglets born from protein-restricted mothers. Moderate maternal protein restriction does however cause significant reduction in intestinal growth in newborn piglets which may decrease the neonatal digestive capacity.
Keywords:IUGR  Insulin  Glucose  Intestine  Pancreas
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