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Identifiers
 ; IGF-I; IGF1A; IGFI
External IDs
:  :  :  :
Molecular function
Cellular component
Biological process
RNA expression pattern
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a
that in humans is encoded by the IGF1 . IGF-1 has also been referred to as a " factor" and its effects were termed "nonsuppressible insulin-like activity" (NSILA) in the 1970s.
IGF-1 is a
similar in
to . It plays an important role in childhood growth and continues to have
effects in adults. A synthetic analog of IGF-1, , is used for the treatment of .
IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges. IGF-1 has a molecular weight of 7,649 daltons.
IGF-1 is produced primarily by the
hormone as well as in target tissues in a paracrine/autocrine fashion. Production is stimulated by
(GH) and can be retarded by undernutrition, growth hormone insensitivity, lack of growth hormone receptors, or failures of the downstream signalling pathway post GH receptor including
and . Approximately 98% of IGF-1 is always bound to one of 6 binding proteins (IGF-BP). , the most abundant protein, accounts for 80% of all IGF binding. IGF-1 binds to IGFBP-3 in a 1:1 molar ratio.[]
IGF-1 is produced throughout life. The highest rates of IGF-1 production occur during the pubertal growth spurt. The lowest levels occur in infancy and old age.[]
3-d model of IGF-1
Protein intake increases IGF-1 levels in humans, independent of total calorie consumption.[] Factors that are known to cause variation in the levels of
(GH) and IGF-1 in the circulation include: genetic make-up, the time of day, age, sex, exercise status, stress levels, nutrition level and body mass index (BMI), disease state, race, estrogen status and
Fasting, including , can reduce IGF-1 levels rapidly and dramatically.[]
Its primary action is mediated by binding to its specific receptor, the
(IGF1R), which is present on many cell types in many tissues. Binding to the IGF1R, a , initiates int IGF-1 is one of the most potent natural activators of the
, a stimulator of cell growth and proliferation, and a potent inhibitor of
.[] IGF-1 binds to at least two cell surface receptors: the
(IGF1R), and the . The
seems to be the "physiologic" receptor – it binds IGF-1 at significantly higher affinity than the IGF-1 that is bound to the insulin receptor. Like the insulin receptor, the IGF-1 receptor is a receptor
– meaning it signals by causing the addition of a phosphate molecule on particular tyrosines. IGF-1 activates the insulin receptor at approximately 0.1 times the potency of insulin. Part of this signaling may be via IGF1R/Insulin Receptor heterodimers (the reason for the confusion is that binding studies show that IGF1 binds the insulin receptor 100-fold less well than insulin, yet that does not correlate with the actual potency of IGF1 in vivo at inducing phosphorylation of the insulin receptor, and hypoglycemia).[]
IGF-1 is a primary mediator of the effects of
(GH). Growth hormone is made in the
gland, is released into the blood stream, and then stimulates the
to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every
in the body, especially skeletal , , , , , , ,
cell, and . In addition to the -like effects, IGF-1 can also regulate
and development, especially in nerve cells, as well as cellular
synthesis.[]
Insulin-like growth factor 1 receptor (IGF-1R) and other tyrosine kinase growth factor receptors signal through multiple pathways. A key pathway is regulated by phosphatidylinositol-3 kinase (PI3K) and its downstream partner, the mammalian target of rapamycin (mTOR). Rapamycins complex with FKBPP12 to inhibit the mTORC1 complex. mTORC2 remains unaffected and responds by upregulating Akt, driving signals through the inhibited mTORC1. Phosphorylation of eukaryotic initiation factor 4e (eif-4E) [4EBP] by mTOR inhibits the capacity of 4EBP to inhibit eif-4E and slow metabolism.[]
Insulin-like growth factor 1 has been shown to bind and interact with all the IGF-1 binding proteins (IGFBPs), of which there are seven: , , , , , , and .[] Some IGFBPs are inhibitory. For example, both
bind IGF-1 at a higher affinity than it binds its receptor. Therefore, increases in serum levels of these two IGFBPs result in a decrease in IGF-1 activity.[]
IGF-1 is closely related to a second protein called "". IGF-2 also binds the IGF-1 receptor. However, IGF-2 alone binds a receptor called the "IGF-2 receptor" (also called the mannose-6 phosphate receptor). The insulin-like growth factor-II receptor (IGF2R) lacks signal transduction capacity, and its main role is to act as a sink for IGF-2 and make less IGF-2 available for binding with IGF-1R. As the name "insulin-like growth factor 1" implies, IGF-1 is structurally related to insulin, and is even capable of binding the insulin receptor, albeit at lower affinity than insulin.
of IGF-1 sharing an identical mature region, but with a different E domain is known as mechano-growth factor (MGF).
This section needs more
or relies too heavily on primary sources. Please review the contents of the section and
if you can. Unsourced or poorly sourced material may be . (September 2014)
Rare diseases characterized by inability to make or respond to IGF-1 produce a distinctive type of growth failure. One such disorder, termed
does not respond at all to
due to a lack of GH receptors. The FDA has grouped these diseases into a disorder called severe primary IGF deficiency. Patients with severe primary IGFD typically present with normal to high GH levels, height below 3 standard deviations (SD), and IGF-1 levels below 3 SD. Severe primary IGFD includes patients with mutations in the GH receptor, post-receptor mutations or IGF mutations, as previously described. As a result, these patients cannot be expected to respond to GH treatment.
People with Laron syndrome have strikingly low rates of cancer and .
that results when the
gland produces excess
(GH). A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called , derived from a distinct type of cell (). It leads to anatomical changes and metabolic dysfunction caused by elevated GH and insulin-like growth factor I (IGF-I) levels.
IGF-1 levels can be measured in the blood in 10-;ng/ml amounts. As levels do not fluctuate greatly throughout the day for an individual person, IGF-1 is used by physicians as a
Interpretation of IGF-1 levels is complicated by the wide normal ranges, and marked variations by age, sex, and pubertal stage. Clinically significant conditions and changes may be masked by the wide normal ranges. Sequential management over time is often useful for the management of several types of pituitary disease, undernutrition, and growth problems.
Patients with severe primary insulin-like growth factor-1 deficiency (IGFD) may be treated with either IGF-1 alone or in combination with .
(brand name Increlex) is a synthetic analog of IGF-1 which is approved for the treatment of . IGF-1 has been manufactured recombinantly on a large scale using both yeast and E. coli.
It is now widely accepted that signaling through the /IGF-1-like
pathway is a significant contributor to the
process in many organisms. This avenue of research first achieved prominence with the work of , who showed that mutations in the
double the lifespan of the roundworm, . Daf-2 encodes the worm's unified /IGF-1-like . Despite the impact of IGF1-like on C. elegans longevity, direct application to mammalian aging is not as clear as mammals do not form dauer-like developmental stages.
Insulin/IGF-1-like signaling is conserved from worms to .
experiments show that mutations that reduce insulin/IGF-1 signaling have been shown, in laboratory conditions, to decelerate the degenerative aging process and extend lifespan in a wide range of organisms, including , ,. Reduced IGF-1 signaling is also thought to contribute to the "anti-aging" effects of .
Therapeutic administration with neurotrophic proteins (IGF I) is associated with potential reversal of degeneration of spinal cord motor neuron axons in certain peripheral neuropathies.
The IGF signaling pathway has a pathogenic role in cancer. Studies have shown that decreased levels of IGF lead to decreased growth of existing cancer cells. People with
have also recently been shown to be of much less risk to develop cancer. Dietary interventions and modifications such as vegan diets shown to down regulate IGF-1 activity, has been associated with lower risk of cancer.
IGF-1 has also been shown to be effective in animal models of stroke when combined with . Both behavioural and cellular improvements were found.
Several companies have evaluated IGF-1 in clinical trials for a variety of indications, including , ,
(ALS aka "Lou Gehrig's Disease"), severe burn injury and myotonic muscular dystrophy (MMD). Results of clinical trials evaluating the efficacy of IGF-1 in type 1 diabetes and type 2 diabetes showed great promise in reducing hemoglobin A1C levels, as well as daily insulin consumption[]. However, the sponsor, , discontinued the program due to an exacerbation of
in patients coupled with a shift in corporate focus towards . Cephalon and Chiron conducted two pivotal clinical studies of IGF-1 for ALS, and although one study demonstrated efficacy, the second was equivocal,[] and the product has never been approved by the FDA.
In a clinical trial of an investigational compound , which raises IGF-1 in patients, did not result in an improvement in patients' Alzheimer's symptoms. Another clinical demonstrated that Cephalon's IGF-1 does not slow the progression of weakness in
patients, but other studies shown strong beneficial effects of IGF-I replacement therapy in ALS patients, and therefore IGF-I may have the potential to be an effective and safe medicine against ALS, however other studies had conflicting results.
Insmed was found to infringe on patents licensed by Tercica, which then sought to get a U.S. district court judge to ban sales of Iplex. To settle patent infringement charges and resolve all litigation between the two companies, in March 2007 Insmed agreed to withdraw Iplex from the U.S. market, leaving Tercica's Increlex as the sole version of IGF-1 available in the United States.
Numerous sources have claimed that , purportedly extracted from cervid sources, contains IGF-1. Credence to this claim comes from the fact that deer's antlers grow extremely rapidly and that the associated cellular factors can similarly aid in skeletal healing in humans. IGF-1 is currently banned by various sporting bodies. However, sprays and pills claiming to be 'deer antler velvet extracts' are freely available on the market. As IGF-1 is a protein, it cannot be absorbed orally since it is rapidly
in the . In September 2013, the headquarters of SWATS, an infamous distributor of deer antler spray and other controversial products, was raided and ordered to shut down by 's
citing "numerous serious and willful violations of Alabama’s deceptive trade practices act".
Anthony Bosch, of the Biogenesis clinic in Miami, Florida, alleged to have supplied and injected New York Yankee Alex Rodriguez with Insulin-like growth factor 1, along with several other performance enhancing drugs.[]
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at the US National Library of Medicine
at Lab Tests Online
recombinant GFP labeled at
1gzr: HUMAN INSULIN-LIKE GROWTH FACTOR; ESRF DATA 
1gzy: HUMAN INSULIN-LIKE GROWTH FACTOR; IN-HOUSE DATA 
1gzz: HUMAN INSULIN-LIKE GROWTH FACTOR; HAMBURG DATA 
1h02: HUMAN INSULIN-LIKE GROWTH FACTOR; SRS DARESBURY DATA 
1h59: COMPLEX OF IGFBP-5 WITH IGF-I 
1imx: 1.8 Angstrom crystal structure of IGF-1 
1pmx: INSULIN-LIKE GROWTH FACTOR-I BOUND TO A PHAGE-DERIVED PEPTIDE 
1wqj: Structural Basis for the Regulation of Insulin-Like Growth Factors (IGFs) by IGF Binding Proteins (IGFBPs) 
2dsp: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins 
2dsq: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins 
2dsr: Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins 
2gf1: SOLUTION STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR 1: A NUCLEAR MAGNETIC RESONANCE AND RESTRAINED MOLECULAR DYNAMICS STUDY 
3gf1: SOLUTION STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR 1: A NUCLEAR MAGNETIC RESONANCE AND RESTRAINED MOLECULAR DYNAMICS STUDY 
3lri: Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I 
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