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

Abstract

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.