Insulin-like Growth Factor-I (IGF-I) and Glutamine Improve Structure and Function in the Small Bowel Allograft

IGF-I, a mitogenic polypeptide hormone, and glutamine (GLN), the preferred enterocyte fuel, singularly improve growth and structure of the small bowel isograft; however, their combined effects on intestinal allografts are unknown. This study examined the effects of IGF-I and GLN, singularly and in combination, on the structure and function of the intestinal allograft. Fifty-nine adult rats underwent resection of the distal 60% of small bowel and received either a 40-cm isograft or an allograft. Either IGF-I (2.4 mg/kg/day) or its vehicle was infused continuously by subcutaneous minipumps. An isocaloric polymeric diet with either 2% GLN or isonitrogenously balanced 2% nonessential amino acids was given continuously by gastrostomy for 10 days. Five groups were studied: isograft (ISO) alone, allograft (ALLO) alone, ALLO and GLN, ALLO and IGF-I, and ALLO and IGF-I with GLN. All recipients received Cyclosporine A (15 mg/kg, im) daily. Mucosal villus height, surface area. crypt depth, IgA, IgG, IgM, and intercellular adhesion molecule-1 (ICAM-I) plasma cells in intestinal tissue, glucose and water absorption of intestinal graft, bacterial translocation (BT) to mesenteric lymph nodes. and body weight were determined. IGF-I increased villus height, surface area ( P < 0.001), crypt depth ( P < 0.01), and glucose absorption ( P < 0.05) compared to the ISO and ALLO groups. GLN increased only crypt depth when compared to the ALLO group ( P < 0.01). Both IGF-I and GLN independently decreased BT to MLN ( P < 0.05) and, in combination, enhanced water absorption ( P < 0.05). There were no significant differences in the number of monoclonal antibody IgA, IgG, and ICAM-1 plasma cells among groups. IgM plasma cells were increased in the IGF-I group compared to the ALLO alone ( P < 0.05). IGF-I and GLN improve function and structure of the small bowel allograft in the rat.