Insulin-like growth factor-binding protein-4 inhibits epithelial growth and proliferation in the rodent intestine.

Insulin-like growth factor-binding protein-4 (IGFBP-4) is a binding protein that modulates the action of insulin-like growth factor-1 (IGF-1), a growth factor whose presence is required for the intestinotrophic effects of glucagon-like peptide-2 (GLP-2). GLP-2 is a gut hormone that uses both IGF-1 and epidermal growth factor (EGF) as intermediary factors to promote intestinal growth. Therefore, to elucidate the mechanism through which IGFBP-4 regulates IGF-1 activity in the intestine, proliferation assays were conducted using rat intestinal epithelial cells (IEC-6).

Current and potential therapeutic targets of glucagon-like peptide-2.

Glucagon-like peptide-2 (GLP-2) is a gut hormone that promotes highly specific growth and function of the intestinal epithelium. Recent studies have begun to elucidate the complex mechanism of action of GLP-2, which is mediated indirectly through other intestinal factors. Although a long-acting GLP-2 analog has recently been approved for treatment of adult patients with short bowel syndrome, there remain numerous conditions characterized by intestinal insufficiency for which pre-clinical studies, as well as some limited clinical data, support further consideration of GLP-2 for expanded therapeutic use.

IGF binding protein-4 is required for the growth effects of glucagon-like peptide-2 in murine intestine.

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone that stimulates the growth of the intestinal epithelium. We have previously demonstrated that GLP-2 exerts its intestinotropic effect through an indirect mechanism that requires both IGF-1 and the intestinal epithelial IGF-1 receptor. However, the biological activity of IGF-1 is modulated by IGF binding proteins (IGFBPs), including IGFBP-4, which is highly expressed in the intestine.