AJP - Gastrointestinal and Liver Physiology, Vol 269, Issue 6 974-G980, Copyright © 1995 by American Physiological Society

ARTICLES

Resection-induced colonic adaptation is augmented by IGF-I and associated with upregulation of colonic IGF-I mRNA

M. P. Mantell, T. R. Ziegler, W. T. Adamson, J. A. Roth, W. Zhang, W. Frankel, A. Bain, J. C. Chow, R. J. Smith and J. L. Rombeau
Department of Surgery, University of Pennsylvania Hospital, Philadelphia 19104, USA.

The effects of exogenous insulin-like growth factor-I (IGF-I) on colonic adaptation were examined in male Sprague-Dawley rats (n = 60, 225-275 mg) after either a 60% small bowel and cecal resection (RX) or mid-small bowel transection with reanastomosis (TX). Animals received a 7-day treatment with either IGF-I (2.4 mg.kg-1.day-1) or vehicle (V; 0.1 mol/l acetic acid). Body weight decreased significantly after resection (-25.6 +/- 4.0 g; P < 0.05 vs. TX/V). IGF-I treatment significantly reduced weight loss after resection (-12.4 +/- 3.8 g; P < 0.01 vs. RX/V) and induced significant weight gain after transection (15.6 +/- 4.0 g; P < 0.05 vs. TX/V). Plasma IGF-I decreased with resection (526 +/- 41 TX/V vs. 344 +/- 17 ng/ml RX/V; P < 0.01). IGF-I treatment significantly increased plasma IGF-I levels (805 +/- 100 ng/ml TX/IGF, 677 +/- 56 ng/ml RX/IGF). After resection, IGF-I treatment significantly increased colonic mucosal weight, DNA, protein content, and crypt depth when compared with resection alone (P < 0.05). Colonic water absorption, measured by an in vivo [3H]polyethylene glycol assay, was significantly increased by IGF-I treatment in resected animals (399 +/- 23 RX/IGF vs. 306 +/- 32 microliter.cm-1.h-1 RX/V; P < 0.05). Resection resulted in increased steady-state colonic IGF-I mRNA (182% of TX/V; P < 0.01) without significantly affecting IGF-I receptor mRNA expression. Regulation of IGF binding protein (BP)-3 and -4 was discoordinate, with IGFBP-3 mRNA tending to decrease with resection (67% of TX/V; P is not significant) and IGFBP-4 increasing significantly (191% of TX/V; P < 0.05). An important role for IGF-I in colonic adaptation after massive intestinal resection is indicated by 1) significantly enhanced colonic mucosal growth and water absorption with IGF-I treatment and 2) postresection upregulation of colonic IGF-I mRNA and alteration of IGFBP-3 and IGFBP-4 mRNA expression.

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