Treatment with IGF-I Peptides Improves Function of the Remnant Gut Following Small Bowel Resection in Rats

Abstract

The effects of 7 days' s.c. infusion of 111-700 μg/day IGF-1 on gut growth and absorptive function were examined in growing rats following removal of 70 or 80% of the jejuno-ileum, and compared with the responses to the analogues, LR3IGF-I and des(1-3)IGF-I, which bind poorly to IGF binding proteins. Administration of 278 μg/day IGF-I, LR3IGF-I or des(1-3)IGF-I following 70% jejuno-ileal resection significantly attenuated malabsorption of fat and nitrogen. Responses in rats with 80% resection were less substantial, but a dose-responsive reduction in malabsorption was apparent with LR3IGF-I. Both IGF-I and LR3IGF-I were shown to increase body weight gain and food conversion efficiency in a dose-dependent manner following 80% jejuno-ileal resection. Total gut weight was increased by up to 21%, due predominantly to increased weight of the stomach and proximal small bowel, with the latter effect attributable at least in part to an increased bowel length. LR3IGF-l was more potent than IGF-l at stimulating body weight gain and food conversion efficiency, but its potency advantage on gut absorptive function and small intestinal re-growth was less marked. We conclude that administration of IGF-l peptides improves gastro-intestinal absorptive function following partial gut resection, most likely reflecting, at least in part, an increase in gut absorptive surface area.