Previously we have demonstrated that TPN alters amino acid and peptide transporter mRNA levels in rat intestine (Howard et al. 2001). We looked at eight different transporters and identified three subgroups: those which showed (i) increased duodenal but not ileal levels during TPN (ATA2, ASCT1 and GLYT1); (ii) increased levels in ileum only (ASCT2, NBAT, EAAC1, PepT1); and (iii) no effect of TPN (CAT1). We have now investigated how co-infusion of the intestino-trophic factor GLP-2 influences these responses.

Rats were established on TPN given into the jugular vein (Hypnorm, 0.1 ml, I.M.) and received no oral intake for 7 days. A second group were given TPN supplemented with GLP-2 (100 mg per rat per day). Orally fed control animals were given saline infusions and had free access to oral diets. After 7 days animals were humanely killed and cDNA was prepared from duodenal and ileal mucosa. mRNA levels, expressed in arbitrary units relative to 18S rRNA, were measured by semi-quantitative polymerase chain reaction.

In both duodenum and ileum GLP-2 abrogated any effects of TPN, maintaining mRNA levels at orally fed control values. For example, compared with orally fed animals, duodenal content of the neutral amino acid transporter ASCT1 mRNA was increased 1.9-fold by TPN but remained unchanged with TPN + GLP-2 co-infusion (orally fed, 1.00 ± 0.09; TPN, 1.87 ± 0.05, P < 0.01; TPN + GLP-2, 0.92 ± 0.1, P > 0.05, means ± S.E.M., n = 6, unpaired t test). Neither TPN nor TPN + GLP-2 had an effect on ileal ASCT1 mRNA level (orally fed, 1.00 ± 0.03; TPN, 0.92 ± 0.04; TPN + GLP-2, 0.85 ± 0.12; P > 0.05). Comparable results were found for ATA2, ASCT2, NBAT and PepT1. However, both GLYT1 and EAAC1 ileal mRNA levels were significantly reduced by TPN + GLP-2 co-infusion when compared with orally fed animals (GLYT1: orally fed, 1.00 ± 0.03, TPN + GLP-2, 0.52 ± 0.07, P < 0.01; EAAC1: orally fed, 1.00 ± 0.06, TPN + GLP-2, 0.62 ± 0.12, P < 0.05).

Co-infusion of GLP-2 during TPN prevents TPN-mediated increases in intestinal amino acid and peptide transporter mRNA levels. This suggests that GLP-2 is involved in maintaining normal intestinal function, and this may be compromised in the absence of enteral nutrition.

This work was funded by BBSRC.

All procedures accord with current UK legislation.