Bio-Rad Human Metabolic and Hormone Assays - Manual (Page 3)

1
Introduction
I nsulin-like growth factors (IGFs), along with their binding proteins (IGFBPs),
have been shown to play key roles in cell growth, organogenesis, and in the
pathophysiology of various cancers. Levels of IGF-1 gradually increase after
birth, peak at puberty, and decline thereafter. Unlike insulin, IGFs circulate
in biological fluids, mostly complexed to IGFBPs. IGF-2 is typically low at
birth and increases with age until puberty, then levels remain unchanged
throughout the rest of life. Serum IGF-2 is roughly twice that of IGF-1
(Meinbach and Lokeshwar 2006). IGFs are regulated by IGFBPs, which bind
the free IGFs to form a ternary complex and modulate IGF binding to the
IGF receptors (IGFRs) on endothelium.
The IGFBPs are divided into high affinity IGFBPs (IGFBP-1 through IGFBP-6)
and low affinity IGFBPs (IGFBP-7 through IGFBP-10). IGFBP-1 through
IGFBP-6 have been well characterized, and are capable of binding both
IGF-1 and IGF-2 with higher affinity than the IGF-IGFR interaction (Juul
2003). Of all the IGFBPs, IGFBP-1 is known to be nutritionally regulated,
with serum levels highest during fasting and lowest postprandial. IGFBP-3
is the most abundant and binds as much as 99% of the circulating IGF
pool (Hjortebjerg and Frystyk 2013). IGFBP-2 is the second most abundant
and, like IGFBP-1, links the IGF system with insulin sensitivity, glucose
metabolism, and cancer. IGFBP-4 is mostly derived from the liver. Its serum
concentration represents less than 10% of IGFBP-3 serum concentration.
Serum levels of IGFBP-4 and IGFBP-6 were found to increase with age
while the opposite was found with IGFBP-5. IGFBP-7 is expressed in a
variety of tissues including heart, spleen, ovary, and intestine. Unlike the
other six members, it has roughly 100-fold lower affinity for IGF-1 while its
affinity for insulin is 500-fold higher (Kutsukake 2008).
The usefulness of serum IGF-1, IGFBP-3, and serum IGF-1/IGFBP-3 molar
ratio is well documented in the diagnosis and treatment of growth and
metabolic disorders, diabetes, cardiovascular diseases, and cancers.