Insulin-like growth factor-I (IGF-I) attenuates jejunal atrophy in association with increased expression of IGF-I binding protein-5 in parenterally fed mice.
Total parenteral nutrition (TPN) induces dramatic mucosal hypoplasia in rat small intestine that is attenuated by insulin-like growth factor-I (IGF-I). Our aim was to determine the extent of TPN-induced intestinal atrophy and its response to infusion of IGF-I in mice. Male C57BL/6 mice (18-22 g) were maintained with TPN, TPN plus co-infusion of recombinant human IGF-I [2.5 mg/(kg . d)] or oral feeding for 5 d. Body weights did not differ among the groups although serum IGF-I was increased by 78% with IGF-I infusion. IGF-I prevented the significant 25% reduction in mass of the intact small intestine due to TPN compared with oral feeding. Greater TPN-induced atrophy was noted in duodenum and jejunum than ileum. Jejunal atrophy induced by TPN reflected significant decreases in muscularis mass and concentrations of protein and DNA; mucosal cellularity was not altered by TPN. TPN induced a significant decrease in jejunal muscularis width that was reversed by IGF-I with no differences in mucosal villus height and crypt depth. Local expression of IGF-I binding protein (IGFBP)-5 positively modulates the intestinotrophic effects of IGF-I. Jejunal atrophy due to TPN and growth due to IGF-I were directly associated with expression of IGFBP-5 mRNA. TPN decreased IGFBP-5 mRNA by 60% and IGF-I increased IGFBP-5 mRNA by 200% with no change in IGF-I mRNA compared with oral feeding. In summary, TPN induces significant 25% atrophy of the mouse small intestine that is attenuated by IGF-I in association with increased expression of IGFBP-5. Compared with rats, TPN-induced atrophy is less severe and occurs primarily in the jejunal muscularis layer in mice.
Murali
Sangita G
SG
University of Wisconsin-Madison, Department of Nutritional Sciences, Madison, WI 53706, USA.
Nelson
David W
DW
Draxler
Angela K
AK
Liu
Xiaowen
X
Ney
Denise M
DM
D000818:Animals; D001835:Body Weight; D015870:Gene Expression; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood / Q000235:genetics* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology; D007422:Intestines / Q000473:pathology; D007583:Jejunum / Q000737:chemistry / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010289:Parenteral Nutrition, Total; D012333:RNA, Messenger / Q000032:analysis; D013393:Sucrase / Q000378:metabolism
D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013393:Sucrase