Insulin-like Growth Factor (IGF) System
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The insulin-like growth factors (IGFs) are polypeptides with high sequence similarity to insulin. The IGF system (also known as IGF axis consists of two ligands (IGF-1 and IGF-2), two cell-surface receptors (IGF1R and IGF2R), a family of six high-affinity IGF binding proteins (IGFBP 1-6), at least four additional low-affinity binding proteins referred to as IGFBP related proteins (IGFBP-rP), as well as a group of enzymes involved in IGFBP degradation. The insulin-like growth factor system plays critical roles in somatic growth in an endocrine fashion (somatomedin hypothesis) as well as proliferation and differentiation of normal and malignant cells in a paracrine/autocrine fashion. Insulin-like growth factor 2 (IGF-2) is thought to be a primary growth factor required for early development while expression of insulin-like growth factor 1 (IGF-1) is required for achieving maximal growth. Insulin-like growth factors act through biding the cell-surface receptors, including IGF1R, IGF2R, the insulin receptor, the insulin-related receptor and possibly other receptors. IGF binding proteins help to modulate IGF action in complex ways that involve both inhibiting IGF action by preventing binding to the IGF-1 receptor as well as promoting IGF action possibly through aiding in delivery to the receptor and increasing IGF half-life. Recent studies have revealed important roles of the insulin-like growth factor system in diseases such as cancer, diabetes and malnutrition.