INSULIN-LIKE GROWTH-FACTOR-I IMPROVES MUCOSAL STRUCTURE AND FUNCTION IN TRANSPLANTED RAT SMALL-INTESTINE

The transplanted small intestine develops significant mucosal atrophy, impaired nutrient and water absorption, and increased bacterial trans location to mesenteric lymph nodes in rats maintained on elemental die ts or total parenteral nutrition, This study determined the effects of administration of an peptide growth factor (insulin-like growth facto r-I[IGF-I]) on the mucosal structure and barrier function of rat small bowel isografts, Thirty-six adult Lewis rats underwent either resecti on of the distal 60% of the small bowel and proximal colon followed by a 40-cm orthotopic jejunal isograft or proximal small bowel transecti on and distal small bowel resection to leave an analogous length of sm all intestine in control animals, Ah rats received an isocaloric, ison itrogenous, polymeric diet (200 kcal/kg/day, 2 gN/kg/day) by gastrosto my and were infused with either IGF-I (2.4 mg/kg/day) or vehicle by os motic pumps subcutaneously. After 10 days of treatment, jejunal crypt cell production, mucosal morphometric indices, glucose and water absor ption, body weight, and bacterial translocation to mesenteric lymph no des (MLN) were measured. Jejunal mRNA content for IGF-I, IGF-I recepto r, and IGF-binding proteins 3 and 4 (IGFBP-3,4) were determined by Nor thern blotting. Crypt cell production, villus height, crypt depth, and villus surface area were significantly increased in control and trans planted jejunum of rats infused with IGF-I when compared to animals gi ven vehicle alone. Additionally, jejunal glucose absorption and water absorption were significantly improved in both IGF-I groups when compa red with their respective vehicle controls. IGF-I infusion increased b ody weight in transplanted and control animals and markedly reduced ba cterial translocation to MLN after small bowel transplantation. Jejuna l levels of IGF-I mRNA were significantly increased in transplanted an imals when compared to transected controls, IGF-I treatment significan tly increased IGFBP-3 tissue mRNA levels in both transected and transp lanted animals. These results demonstrate that IGF-I administration, a fter small bowel transplantation, improves mucosal structure and absor ptive function and reduces bacterial translocation to MLN. IGF-I may h ave important effects in transplanted small bowel both as an endogenou s and administered growth factor.