Intestinotrophic effects of exogenous IGF-I are not diminished in IGF binding protein-5 knockout mice.
IGF binding protein-5 (IGFBP-5) modulates the availability of IGF-I to its receptor and potentiates the intestinotrophic action of IGF-I. Our aim was to test the hypothesis that stimulation of intestinal growth due to coinfusion of IGF-I with total parenteral nutrition (TPN) solution is dependent on increased expression of IGFBP-5 through conducting our studies in IGFBP-5 knockout (KO) mice. IGFBP-5 KO, heterozygote (HT) and wild type (WT) male and female mice were maintained with TPN or TPN plus coinfusion of IGF-I [recombinant human (rh)IGF-I; 2.5 mg x kg(-1) x day(-1)] for 5 days. The concentration of IGF-I in serum was 73% greater (P < 0.0001) in mice given TPN + IGF-I infusion compared with TPN alone. IGF-I attenuated the 2-3 g loss of body weight associated with TPN in WT mice, whereas KO and HT mice did not show improvement in body weight with IGF-I treatment. KO and HT mice had significantly greater levels of circulating IGF-I binding proteins (IGFBPs) compared with WT mice. Intestinal growth due to IGF-I was observed in all groups treated with IGF-I based on greater concentrations of protein and DNA in small intestine and colon and significantly greater crypt depth and muscularis thickness in jejunum. Jejunal expression of IGFBP-5 mRNA was greater in WT mice, whereas IGFBP-3 mRNA was greater in KO mice treated with IGF-I. In summary, the absence of the IGFBP-5 gene did not block the ability of IGF-I to stimulate intestinal growth, possibly because greater jejunal expression of IGFBP-3 compensates for the absence of IGFBP-5.
Murali
Sangita G
SG
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsinn 53706, USA.
Liu
Xiaowen
X
Nelson
David W
DW
Hull
Angela K
AK
Grahn
Michael
M
Clayton
Murray K
MK
Pintar
John E
JE
Ney
Denise M
DM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D007422:Intestines / Q000187:drug effects* / Q000254:growth & development*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding
D018975:Insulin-Like Growth Factor Binding Protein 5; D007334:Insulin-Like Growth Factor I