While IGF-1 has very complex functions, it appears largely
to mediate the actions of growth hormone. Thus, IGF-1 is important in prenatal
development, growth to adulthood and metabolic control. It induces amino acid
uptake, protein synthesis and glucose utilization. It is an important mitogen
and regulator of the cell cycle and apoptosis. IGF-1 is produced primarily by
hepatocytes, serving an endocrine function. It is also produced by many other
cells, where it may act in an autocrine or paracrine manner. Serum levels of
IGF-1 have been reported to increase from birth to puberty, followed by a slow
decline through adulthood.
There are two receptors for the IGFs; type I IGF receptor,
which signals through a tyrosine kinase, and type II IGF receptor, which is
identical to the mannose-6-phosphate receptor and may not signal. The action of
IGF on its receptors is very complex, with control by at least six IGF-binding
proteins (IGFBP-1 through IGFBP-6). IGFBP-3 binds over 90% of the total IGF in
serum in a complex of IGF, IGFBP and an acid-labile subunit. This ternary
complex greatly stabilizes IGF in the circulation, changing the half life from
minutes to hours. In addition, IGFBPs modulate the action of IGF on the
membrane receptors. Adding to the complexity is a family of proteases that act
on IGFBPs, modifying their affinity for IGF or completely eliminating the
IGFBPs. The interactions of IGF, IGFBP, IGFBP proteases, and IGF receptors are
referred to as the IGF axis. The IGF axis affects many primary physiological
and pathological processes, including development, growth, metabolic regulation,
tumorigenesis, atherosclerosis and angiogenesis.
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