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Department of Nutritional Sciences (D.M.N., D.J.H., M.B.G., K.R.K., E.M.D.), University of Wisconsin-Madison, Madison, Wisconsin 53706; and Department of Biochemistry (J.L.T., M.L.A.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284
Address all correspondence and requests for reprints to: Denise M. Ney, Ph.D., Department of Nutritional Sciences, University of Wisconsin-Madison, 1415 Linden Drive, Madison, Wisconsin 53706. E-mail: ney{at}nutrisci.wisc.edu
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 parenteral nutrition (TPN) and treated with rhIGF-I and/or rhGH. TPN without growth factor treatment (TPN control) induced jejunal atrophy, reduced serum IGF-I, increased serum insulin concentrations, and increased IGF-I receptor number, IGF-I receptor messenger RNA, and insulin-specific binding to 133% to 170% of the orally fed reference values, P < 0.01. Compared with TPN control, IGF-I or IGF-I + GH stimulated jejunal mucosal hyperplasia; IGF-I treatment 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 content. Treatment with GH alone increased serum IGF-I concentration, did not alter TPN-induced jejunal atrophy, and decreased insulin-specific binding and insulin receptor protein content (39% and 59%, respectively, of the TPN control values, P < 0.01). We conclude that: 1) jejunal IGF-I receptor content reflects circulating concentration of ligand and is not limiting for jejunal growth; and 2) increased circulating concentration of IGF-I may promote jejunal growth via interaction with jejunal insulin or IGF-I receptors.
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