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
Jane C.-J. Chao;Sharon Donovan Chao JCJ and Donovan S
Abstract
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 5nM and insulin at 700nM (IEC-6) or 1400nM (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(superscript r) of 28.5kDa, while FHs cells secreted several IGFBPs with M(superscript r) from 43 to 24kDa.
Mitogenic activity of IGF-I at 5nM was equal to des-IGF-I at 0.005nM, 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.
