Increased expression of specific intestinal amino acid and peptide transporter mRNA in rats fed by TPN is reversed by GLP-2.
Intestinal function depends on the presence of luminal nutrients and is altered during starvation and refeeding. Amino acids are essential for enterocytes, but the luminal supply is compromised with changes in dietary intake. To test the hypothesis that during periods of restricted luminal nutrient availability mucosal cells undergo adaptations aimed toward preserving amino acid supply, the expression of amino acid and peptide transporter mRNAs was quantified in rats with no oral intake, whose nutritional status was maintained with total parenteral nutrition (TPN). The role of the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) was investigated in the adaptive responses. Rats were administered TPN with or without exogenous GLP-2. Amino acid and peptide transporter mRNAs in small intestine mucosa were measured by semiquantitative RT-PCR. Compared with orally fed rats, removal of luminal nutrition increased the expression of ASCT1, SAT2, and GLYT1 mRNAs in the duodenum and of ASCT2, EAAC1, NBAT, and PepT1 mRNAs in the ileum. CAT1, PAT1, and SN2 mRNA abundances were unaffected. GLP-2 reversed these effects. Three subgroups of transporters were identified by regional differences in response to TPN. This may reflect differing roles for substrates of transporters located apically and basally and along the proximal-distal axis of the intestine. The importance of maintaining amino acid supply for intestinal mucosal cells is illustrated.
Howard
Alison
A
Institute for Cell and Molecular Biosciences, University of Newcastle Medical School, Newcastle upon Tyne, UK.
Goodlad
Robert A
RA
Walters
Julian R F
JR
Ford
Dianne
D
Hirst
Barry H
BH
D026905:Amino Acid Transport Systems / Q000235:genetics*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D007413:Intestinal Mucosa / Q000737:chemistry*; D007421:Intestine, Small / Q000737:chemistry; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D010289:Parenteral Nutrition, Total; D010455:Peptides / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D026905:Amino Acid Transport Systems; D053767:Glucagon-Like Peptide 2; D026901:Membrane Transport Proteins; D010455:Peptides; D012333:RNA, Messenger; C067802:intestinal peptide-proton cotransporter; D004763:Glucagon-Like Peptides