An EGFR raf-dependent mechanism is necessary for Ras but not for src transformation of intestinal epithelial cells. Polyamines (putrescine, spermidine and sperminine) are involved in DNA, RNA and protein synthesis and thus the polyamines are essential for cell proliferation and growth. Putrescine is taken up from the systemic circulation by the small bowel and is converted to succinate. Uptake and conversion increase with fasting, suggesting that putrescine may be an energy source for the small intestine. ODC is the rate-limiting enzyme of polyamine synthesis. ODC activity is higher and more putrescine is found in the nonproliferating epithelial cells of the villi than in the crypts. Prefeeding after a fast markedly increases the ODC activity in the intestine, with the greatest activity occurring in the villus tip cells and at the villus-crypt junctional area. Exogenous but not de novo-formed histamine competes with putrescine incorporation into enterocyte as catalyzed by transglutaminase activity.
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IGF is a class of low molecular weight growth-promoting peptides. IGF-1 and IGF-2 are present in a variety of biological fluids, including mammalian milk. IGF is stable in the lumen of the intestine, and this stability increases with age. This raises the possibility that milk-borne IGF has biological activity in the intestine. The intestinal atrophy that occurs with TPN can be reduced by IGF-I but not by GH. IGF-1 but not GH stimulates crypt cell proliferation. IGF-I and GH independently and synergistically stimulate one of the IGF binding protein mRNAs. GLP-2 plus either GH or IGF-I causes a greater increase in histological parameters of small intestinal growth in mice than does GLP-2 alone.
GLP-2 promotes intestinal epithelial proliferation by increasing the crypt cell proliferation rate, and by decreasing the enterocyte apoptotic rate. The administration of GLP-2 to mice for 10 days increases small intestinal weight RNA and protein content, and increases the activities of maltase, sucrase, lactate and other brush border enzymes.