Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-I administration.
Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gln) or by administration of insulin-like growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gln and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gln or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gln and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gln diet. Ileal DNA content was highest when IGF-I was administered together with Gln supplementation. Combined IGF-I plus Gln synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gln than observed when IGF-I or Gln was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gln feeding. In contrast, dietary Gln, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gln have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection.
Ziegler
T R
TR
Joslin Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Mantell
M P
MP
Chow
J C
JC
Rombeau
J L
JL
Smith
R J
RJ
D000818:Animals; D004750:Enteral Nutrition; D005527:Food, Fortified; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D006965:Hyperplasia; D007082:Ileum / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology*; D007421:Intestine, Small / Q000502:physiology* / Q000601:surgery; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005973:Glutamine; D007334:Insulin-Like Growth Factor I