Insulin-like growth factor binding proteins in the human circulation: a review.
The actions and bioavailability of the insulin-like growth factors (IGFs) are regulated by a family of six IGF binding proteins. IGFBP-3, the major circulating IGFBP, is unique in combining with a glycoprotein, the acid-labile subunit (ALS), to form a ternary complex with IGF-I or IGF-II. Each component of this trimer is growth hormone-dependent, and the hypoglycemic potential of circulating IGFs appears neutralized in this form. IGFs in the complex have a greatly extended circulating half-life, their stability being conferred by the presence of ALS, which is itself very stable in the circulation. IGFBP-1 does not appear to be a carrier of IGFs, but to act as an acute modulator of their metabolic activities. In this role it can be viewed as an insulin counter-regulator, blocking 'free' insulin-like activity during fasting or hypoglycemia. IGF-I administration causes complex changes in circulating IGFBPs, so that a detailed knowledge of their regulation is essential if the therapeutic potential of IGF-I is to be optimised.
Baxter
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RC
Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia.
D000328:Adult; D000818:Animals; D001682:Biological Availability; D002352:Carrier Proteins / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D015394:Molecular Structure; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II