Regulation and actions of the insulin-like growth factor binding proteins

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Six structurally distinct binding proteins for the insulin-like growth factors (IGFs) have been identified. The IGF binding proteins (IGFBPs), IGFBP-1 through IGFBP-6, modulate the Bioavailability and actions of IGFs in the circulation and the extracellular environment. IGFBP-1 is metabolically regulated and suppressed by insulin administration, except when hypoglycemia ensues. IGFBP-3 is the major IGF carrier in serum, where it is found complexed with an acid-labile glycoprotein. The roles of IGFBP-2 and other circulating IGFBPs are as yet poorly defined. Most cell types secrete IGFBPs, with fibrobiasts, hepatocytes, osteobiasts. and granulosa cells being particularly well-studied sources. The actions of IGFBPs in local IGF regulation are complex and are modified by limited proteolysis, phosphorylation, and other posttranslational events. The current intense research focus on the IGF-IGFBP axis will lead to a better understanding of the regulation of IGF action in ceil growth and metabolism and allow the therapeutic utility of the IGFs to be optimized.

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