TREATMENT WITH IGF-I PEPTIDES IMPROVES FUNCTION OF THE REMNANT GUT FOLLOWING SMALL-BOWEL RESECTION IN RATS

The effects of 7 days' s.c. infusion of 111-700 mu g/day IGF-I 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 respo nses to the analogues, LR(3)IGF-I and des(1-3)IGF-I, which bind poorly to IGF binding proteins. Administration of 278 mu g/day IGF-I, LR(3)I GF-I or des(1-3)IGF-I following 70% jejuno-ileal resection significant ly attenuated malabsorption of fat and nitrogen. Responses in rats wit h 80% resection were less substantial, but a dose-responsive reduction in malabsorption was apparent with LR(3)IGF-I. Both IGF-I and LR(3)IG F-I were is shown to increase-body weight gain and food conversion eff iciency in a dose-dependent manner following 80% jejuno-ileal resectio n. Total gut weight was increased by up to 21%, due predominantly to i ncreased weight of the stomach and proximal small bowel, with the latt er effect attributable at least in part to an increased bowel length. LR(3)IGF-I was more potent than IGF-I at stimulating body weight gain and food conversion efficiency, but its potency advantage on gut absor ptive function and small intestinal re-growth was less marked. We conc lude that administration of IGF-I peptides improves gastro-intestinal absorptive function following partial gut resection, most likely refle cting, at least in part, an increase in gut absorptive surface area.