Effects of Insulin, Insulin-Like Growth Factors and Epidermal Growth Factor on Mitogenesis and Disaccharidase Activity in Rat (IEC-6) and Human (FHs 74 Int) Intestinal Cells

Proliferation and differentiation of rat (IEC-6) and human (FHs) small intestinal cells in the presence of epidermal growth factor (EGF), insulin, insulin-like growth factor (IGF)-I, -II, and des[1-3]tripeptide-IGF-I (des-IGF-I) were examined. Thymidine incorporation into IEC-6 cells was significantly increased by insulin, IGF-I, des-IGF-I, IGF-II, and IGF-I + EGF, but not by EGF alone. In contrast, thymidine incorporation into FHs cells was increased only by insulin, IGF-I, and the combination of IGF-I and EGF. Mitogenic activities of IGF-I at 5 nM and insulin at 700 nM (IEC-6) or 1400 nM (FHs) were equivalent, suggesting that both acted through the type I IGF receptor in both cells. IEC-6 cells secreted consistently one predominant IGF binding protein (IGFBP) with M_r of 28.5 kDa, while FHs cells secreted several IGFBPs with M_r from 43 to 24 kDa. Mitogenic activity of IGF-I at 5 nM was equal to des-IGF-I at 0.005 nM, indicating that endogenously produced IGFBPs likely inhibit IGF-I action. In IEC-6 cells, IGFBP-2 secretion, but not mRNA expression, was decreased by EGF and IGF-I+EGF treatments, suggesting post-transcriptional regulation. IGF-II and EGF were more potent than IGF-I at increasing maltase and sucrase activities, suggesting that these growth factors may stimulate differentiation to a greater degree than mitogenesis.