Investigation of insulin-like growth factor (IGF)-I and insulin receptor binding and expression in jejunum of parenterally fed rats treated with IGF-I or growth hormone

To investigate the ability of insulin-like growth factor-I (IGF-I), but not GH, to stimulate jejunal growth, we compared indices of IGF-I and insulin receptor expression in jejunal membranes from rats maintained with total pa renteral nutrition (TPN) and treated with rhIGF-I and/or rhGH. TPN without growth factor treatment (TPN control) induced jejunal atrophy, reduced seru m IGF-I, increased serum insulin concentrations, and increased IGF-I recept or number, IGF-I receptor messenger RNA, and insulin-specific binding to 13 3% to 170% of the orally fed reference values, P < 0.01. Compared with TPN control, IGF-I or IGF-I + GH stimulate jejunal mucosal hyperplasia; IGF-I t reatment increased serum IGF-I by 2- to 3-fold and decreased serum insulin concentrations by 60%, decreased IGF-I receptor number by 50% (P < 0.001), and increased insulin receptor affinity and insulin receptor protein conten t. Treatment with GH alone increased serum IGF-I concentration, did not alt er TPN-induced jejunal atrophy, and decreased insulin-specific binding and insulin receptor protein content (39% and 59%, respectively, of the TPN con trol values, P < 0.01). We conclude that: 1)jejunal IGF-I receptor content reflects circulating concentration of ligand and is not limiting for jejuna l growth; and 2) increased circulating concentration of IGF-I may promote j ejunal growth via interaction with jejunal insulin or IGF-I receptors.