Investigation of insulin-like growth factor (IGF)-I and insulin receptor binding and expression in jejunum of parenterally fed rats treated with IGF-I or growth hormone.
To investigate the ability of insulin-like growth factor-I (IGF-I), but not GH, to stimulate jejunal growth, we compared indices of IGF-I and insulin receptor expression in jejunal membranes from rats maintained with total parenteral nutrition (TPN) and treated with rhIGF-I and/or rhGH. TPN without growth factor treatment (TPN control) induced jejunal atrophy, reduced serum IGF-I, increased serum insulin concentrations, and increased IGF-I receptor number, IGF-I receptor messenger RNA, and insulin-specific binding to 133% to 170% of the orally fed reference values, P < 0.01. Compared with TPN control, IGF-I or IGF-I + GH stimulated jejunal mucosal hyperplasia; IGF-I treatment increased serum IGF-I by 2- to 3-fold and decreased serum insulin concentrations by 60%, decreased IGF-I receptor number by 50% (P < 0.001), and increased insulin receptor affinity and insulin receptor protein content. Treatment with GH alone increased serum IGF-I concentration, did not alter TPN-induced jejunal atrophy, and decreased insulin-specific binding and insulin receptor protein content (39% and 59%, respectively, of the TPN control values, P < 0.01). We conclude that: 1) jejunal IGF-I receptor content reflects circulating concentration of ligand and is not limiting for jejunal growth; and 2) increased circulating concentration of IGF-I may promote jejunal growth via interaction with jejunal insulin or IGF-I receptors.
Ney
D M
DM
Department of Nutritional Sciences, University of Wisconsin-Madison, 53706, USA. ney@nutrisci.wisc.edu
Huss
D J
DJ
Gillingham
M B
MB
Kritsch
K R
KR
Dahly
E M
EM
Talamantez
J L
JL
Adamo
M L
ML
D000818:Animals; D013006:Growth Hormone / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology*; D007583:Jejunum / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010288:Parenteral Nutrition; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D011972:Receptor, Insulin