Insulin-like growth factor

<h2 id="igf1gh-axis">IGF1/GH axis</h2>
The IGF "axis" is also commonly referred to as the Growth Hormone/IGF-1 Axis. <a href="/facts/Insulin-like_growth_factor_1/2n0nPvtD">Insulin-like growth factor 1</a> (commonly referred to as IGF-1 or at times using <a href="/facts/Roman_numerals/7BA8nn78">Roman numerals</a> as IGF-I) is mainly secreted by the liver as a result of stimulation by <a href="/facts/Growth_hormone/SLEJ1fws">growth hormone</a> (GH). IGF-1 is important for both the regulation of normal physiology, as well as a number of pathological states, including <a href="/facts/Cancer/PVW6n1D0">cancer</a>. The IGF axis has been shown to play roles in the promotion of <a href="/facts/Cell_proliferation/Jp3hWo2t">cell proliferation</a> and the inhibition of <a href="/facts/Cell_death/UYCzvewT">cell death</a> (<a href="/facts/Apoptosis/8dVzSm4y">apoptosis</a>). 
<a href="/facts/Insulin-like_growth_factor_2/HnxTYloa">Insulin-like growth factor 2</a> (IGF-2, at times IGF-II) is thought to be a primary <a href="/facts/Growth_factor/D1xnRbcH">growth factor</a> required for early development while <a href="/facts/IGF-1/2n0nPvtD">IGF-1</a> expression is required for achieving maximal growth. <a href="/facts/Gene_knockout/RJTMDbUR">Gene knockout</a> studies in mice have confirmed this, though other animals are likely to regulate the expression of these genes in distinct ways. While IGF-2 may be primarily <a href="/facts/Fetus/evocHd0Y">fetal</a> in action it is also essential for development and function of organs such as the <a href="/facts/Brain/EKla9NkJ">brain</a>, <a href="/facts/Liver/Rtp4Fk2b">liver</a>, and <a href="/facts/Kidney/HBspPrv9">kidney</a>.<a class="footnote-ref" id="fnref:1" href="#fn:1">1</a>
Factors that are thought to cause variation in the levels of GH and IGF-1 in the circulation include an individual's genetic make-up, the time of day, age, sex, exercise status, stress levels, nutrition level, <a href="/facts/Body_mass_index/UX4YrUTx">body mass index</a> (BMI), disease state, race, estrogen status, and <a href="/facts/Xenobiotic/0M2LAyEx">xenobiotic</a> intake.<a class="footnote-ref" id="fnref:2" href="#fn:2">2</a><a class="footnote-ref" id="fnref:3" href="#fn:3">3</a><a class="footnote-ref" id="fnref:4" href="#fn:4">4</a>
IGF-1 has an involvement in regulating <a href="/facts/Neural_development/hSjrUxCn">neural development</a> including <a href="/facts/Neurogenesis/XSteTv8s">neurogenesis</a>, <a href="/facts/Myelination/DKgJB8s8">myelination</a>, <a href="/facts/Synaptogenesis/1fVRWK6e">synaptogenesis</a>, and <a href="/facts/Dendrite/bwv8MABY">dendritic</a> branching and <a href="/facts/Neuroprotection/BcbsTfN0">neuroprotection</a> after neuronal damage. Increased serum levels of IGF-I in children have been associated with higher <a href="/facts/IQ/rozfcXsk">IQ</a>.<a class="footnote-ref" id="fnref:5" href="#fn:5">5</a>
IGF-1 shapes the development of the <a href="/facts/Cochlea/J2ozV2sP">cochlea</a> through controlling <a href="/facts/Apoptosis/8dVzSm4y">apoptosis</a>. Its deficit can cause <a href="/facts/Hearing_(sense)/EPYrVkSx">hearing</a> loss. Serum level of it also underlies a correlation between short <a href="/facts/Human_height/MBr7rrUy">height</a> and reduced hearing abilities particularly around 3–5 years of age, and at age 18 (late <a href="/facts/Puberty/vjfPAKf4">puberty</a>).<a class="footnote-ref" id="fnref:6" href="#fn:6">6</a>

<h2 id="igf-receptors">IGF receptors</h2>
Main article: <a href="/facts/Insulin-like_growth_factor_receptor/fAXcI7Uz">Insulin-like growth factor receptor</a>
The IGFs are known to bind the <a href="/facts/IGF-1_receptor/R4c7MCqp">IGF-1 receptor</a>, the <a href="/facts/Insulin_receptor/PCEbQj6k">insulin receptor</a>, the <a href="/facts/Insulin-like_growth_factor_2_receptor/f4v8L7N0">IGF-2 receptor</a>, the insulin-related receptor and possibly other receptors. The IGF-1 receptor is the "physiological" receptor. <a href="/facts/IGF-1/2n0nPvtD">IGF-1</a> binds to it at significantly higher affinity than it binds the insulin receptor. Like the insulin receptor, the IGF-1 receptor is a <a href="/facts/Receptor_tyrosine_kinase/1oNWIdV8">receptor tyrosine kinase</a>—meaning the receptor signals by causing the addition of a phosphate molecule on particular tyrosines. The IGF-2 receptor only binds IGF-2 and acts as a "clearance receptor"—it activates no intracellular signaling pathways, functioning only as an IGF-2 sequestering agent and preventing IGF-2 signaling.<a class="footnote-ref" id="fnref:7" href="#fn:7">7</a>

<h2 id="organs-and-tissues-affected-by-igf-1">Organs and tissues affected by IGF-1</h2>
Since many distinct tissue types express the IGF-1 receptor, IGF-1's effects are diverse. It acts as a <a href="/facts/Neurotrophic/bJNG05TQ">neurotrophic</a> factor, inducing the survival of neurons. It may catalyse <a href="/facts/Skeletal_muscle/en1tVYFN">skeletal muscle</a> <a href="/facts/Hypertrophy/4JolPfnS">hypertrophy</a>, by inducing <a href="/facts/Protein_synthesis/P4IcGjPd">protein synthesis</a>, and by blocking <a href="/facts/Muscle_atrophy/WgJ9jhKw">muscle atrophy</a>. It is protective for <a href="/facts/Cartilage/vxy2qzKN">cartilage</a> cells, and is associated with activation of <a href="/facts/Osteocytes/nUBl8e1S">osteocytes</a>, and thus may be an anabolic factor for <a href="/facts/Bone/kwJaR6IQ">bone</a>. Since at high concentrations it is capable of activating the <a href="/facts/Insulin_receptor/PCEbQj6k">insulin receptor</a>, it can also complement for the effects of <a href="/facts/Insulin/oXG0myt1">insulin</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8">8</a> Receptors for IGF-1 are found in vascular smooth muscle, while typical receptors for insulin are not found in vascular smooth muscle.<a class="footnote-ref" id="fnref:9" href="#fn:9">9</a>

<h2 id="igf-binding-proteins">IGF-binding proteins</h2>
IGF-1 and IGF-2 are regulated by a family of proteins known as the <a href="/facts/Insulin-like_growth_factor-binding_protein/0VaxxlPl">IGF-binding proteins</a>. These proteins help to modulate IGF action in complex ways that involve both inhibiting IGF action by preventing binding to the IGF-1 receptor as well as promoting IGF action possibly through aiding in delivery to the receptor and increasing IGF half-life. Currently, there are seven characterized IGF Binding Proteins (IGFBP1 to IGFBP7). There is currently significant data suggesting that IGFBPs play important roles in addition to their ability to regulate IGFs.
IGF-1 and IGFBP-3 are GH dependent, whereas IGFBP-1 is insulin regulated.
IGFBP-1 production from the liver is significantly elevated during insulinopenia while serum levels of bioactive IGF-1 is increased by insulin.<a class="footnote-ref" id="fnref:10" href="#fn:10">10</a>

<h2 id="diseases-affected-by-igf">Diseases affected by IGF</h2>
Studies of recent interest show that the Insulin/IGF axis play an important role in <a href="/facts/Senescence/AHmBEpe8">aging</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11">11</a> <a href="/facts/Nematode/yLMJ43Eu">Nematodes</a>, <a href="/facts/Drosophila_melanogaster/KtnHVCcB">fruit-flies</a>, and other organisms have an increased life span when the gene equivalent to the mammalian insulin is <a href="/facts/Gene_knockout/RJTMDbUR">knocked out</a>. It is somewhat difficult to relate this finding to the mammals, however, because in the smaller organism there are many genes (at least 37 in the nematode Caenorhabditis elegans<a class="footnote-ref" id="fnref:12" href="#fn:12">12</a>) that are "insulin-like" or "IGF-1-like", whereas in the mammals insulin-like proteins comprise only seven members (<a href="/facts/Insulin/oXG0myt1">insulin</a>, IGFs, <a href="/facts/Relaxin/IKrUlbwe">relaxins</a>, EPIL, and relaxin-like factor).<a class="footnote-ref" id="fnref:13" href="#fn:13">13</a> The human insulin-like genes have apparently distinct roles with some but less crosstalk presumably because there are multiple insulin-receptor-like proteins in humans. Simpler organisms typically have fewer receptors; for example, only one insulin-like receptor exists in the nematode C. elegans.<a class="footnote-ref" id="fnref:14" href="#fn:14">14</a> Additionally, C. elegans do not have specialized organs such as the (<a href="/facts/Islets_of_Langerhans/PJVtM7MY">Islets of Langerhans</a>), which sense insulin in response to glucose homeostasis. Moreover, IGF1 affects lifespan in nematodes by causing <a href="/facts/Dauer_larva/nxCgdPGj">dauer</a> formation, a developmental stage of C. elegans larva. There is no mammalian correlate. Therefore, it is an open question as to whether either IGF-1 or insulin in the mammal may perturb aging, although there is the suggestion that dietary restriction phenomena may be related.<a class="footnote-ref" id="fnref:15" href="#fn:15">15</a>
Other studies are beginning to uncover the important role the IGFs play in diseases such as <a href="/facts/Cancer/PVW6n1D0">cancer</a> and <a href="/facts/Diabetes/2xeHXbsI">diabetes</a>, showing for instance that IGF-1 stimulates growth of both prostate and breast cancer cells. Researchers are not in complete agreement about the degree of cancer risk that IGF-1 poses.<a class="footnote-ref" id="fnref:16" href="#fn:16">16</a>

<h2 id="see-also">See also</h2>
<ul><li><a href="/facts/Growth_hormone_treatment/2LMVbN2W">Growth hormone treatment</a></li>
<li><a href="/facts/HGH_controversies/xJRgxlvR">HGH controversies</a></li>
<li><a href="/facts/Insulin%2fIGF%2fRelaxin_family/hTh2rB4p">Insulin/IGF/Relaxin family</a></li></ul>

<h2 id="references">References</h2>

<ol>
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</ol>

Insulin-like growth factor open-in-new

Insulin-like growth factor