The protein Insulin-like Growth Factor 1 (IGF-1) is a liver protein that shows many similarities to Insulin. The two molecules have around sixty percent similarities in their structures, and are released under similar circumstances into the bloodstream. IGF-1 acts as the main growth factor to insulin, acting as the nutrition for cells. The similarities between the two molecules allows for easy transportation of IGF-1 through the bloodstream. As insulin is released into the blood upon hyperglycemic conditions, IGF-1 is released upon excess protein intake and will transport the proteins to cells where it can be used for growth. IGF-1 release can also be stimulated by secretion of Growth Hormone, which induces the protein to deliver nutrients to cells. This process occurs extensively throughout puberty of children. Additionally, after puberty, IGF-1 can be regulated by the release of GH but not to the level of that during puberty and can regularly be secreted without GH stimulus. There have been recent studies showing the biological necessity for IGF-1, as well as the costs of having low levels of this protein which range from reduced cell growth to dysfunctions of particular cells.
Structural highlights
The molecular structure of tell us many things about the protein itself. Upon inspection of the structure of the IGF-1 protein side by side with , there are three noticeable alpha helixes that are almost identical throughout the backbones of the molecules. The IGF-1 protein, being a relatively small molecule with only sixty-nine amino acids, is larger than the insulin molecule (which only has a 51 amino acid sequence). Because of the relatively small size of these molecules, they are easily transported out of the liver and pancreas into the blood and throughout the body. However, unlike insulin which is produced and stored as a hexamer containing six insulin monomers, IGF-1 is produced and stored as a monomer. Because of the structural similarities to insulin, upon the release of IGF-1 from the liver, it can bind to its own transmembrane receptors called (IGF-1R) on cells but can also bind to the insulin receptor depending on biological conditions. Because of their structural similarities, in conditions where insulin is not present or in reduced amounts IGF-1 can bind to both insulin receptors and its own. This also works for insulin, where in conditions of low IGF-1, it can bind to both its own receptors and IGF-1R.
Function
Insulin-like Growth Factor 1 primarily functions as an anabolic promoter. This molecule is produced in bulk in the liver, but most muscles and bones have a local supply of the protein. This means that the range of its application are not limited to only skeletal muscle growth, but overall growth of the body. The secretion of IGF-1 is dependent largely on diet including calories and protein intake. After reducing caloric intake by fifty percent, the resulting IGF-1 levels were significantly decreased. Remarkably, upon reducing protein intake by twenty-five percent brought equal decreases in IGF-1 as the fifty percent decrease in calories. However, when the body is in a surplus of nutrients such as proteins and calories, IGF-1 binds to IGF-1 Receptors (IGF-1R) on cells throughout the body, signaling to the cells to uptake nutrients from the bloodstream and use them to grow. The role of IGF-1 in growth correlates strongly with GH, in that both factors play a vital role in signaling to the body to grow. GH upon release will signal to cells to expand and grow, but to do this on a large scale requires the help of IGF-1. When GH is released, the liver is stimulated to release IGF-1 into the blood to communicate with the various cells of the body. The presence of IGF-1 signals to the cells, stimulating protein synthesis within the cells which provide the energy to grow, and inhibiting protein degradation. With adequate nutrition, these cellular conditions allow for substantial growth of the body, as observed during puberty.
Deficiencies
The role of IGF-1 includes a large part in growth of tissues throughout the body, but in the cases of insufficient levels of this protein, the body cannot produce the standard amount of growth experienced by most people. While complications with this protein are relatively rare, the effects of deficiencies in IGF-1 are substantial. When people cannot organically produce Growth Hormone, the term Laron Syndrome (LS) is given to describe their condition and is an extremely rare diagnosis. Because of their inability to produce GH, there is a correlation with the inability to generate IGF-1 that prevents the body from being able to produce the growth that it needs throughout life. Newborns for instance, if born with LS, are slightly shorter than healthy newborns. Throughout childhood, the child will show a wide range of symptoms. Growth impairment symptoms may include a lack of skeletal maturation, and organ growth including a smaller brain, cardiomicria (small heart), acromicria (small facial, hand and feet bones due to underdevelopment). LS also causes potential for a weakened muscular system which can result in damaged and weakened hair and nails. If left untreated throughout their life, subjects with LS develop dwarfism causing their final height to be between 100 and 145 centimeters, with a highly unproportional upper body to a smaller lower body. However, with treatment, teams have been able to increase the average growth per year in patients with LS. One study showed that daily injections of IGF-1 that is identical to the patient’s own can nearly double the growth of patients in the first year compared to those untreated. The following two years also bring increased growth compared to untreated patients, but not only around 1.5 times. After treatment concluded, some parties reported their patients as reaching a normal final height for their age [1]. Another study on mice showed very similar results upon the intervention of the IGF-1 present in prenatal development. This study showed that as the IGF-1 protein levels are decreased, the weight of the mice upon birth were between sixty and forty-five percent of normal weight of the wild type mice. However, upon intervention on GH during prenatal development, mice with reduced GH were birthed with normal weights [2]. These studies show the impact of IGF-1 in the early stages of development and speaks to its importance for growth throughout human life. Although LS is an extremely rare disorder where the body does not organically produce GH of IGF-1, low levels of GH and IGF-1 are much more common in society and have their own treatment options.
In otherwise normal children and adults, low levels of the protein IGF-1 can result in a range of complications. The deficiency of IGF-1 is typically presented as Adult Growth Hormone Deficiency (AGHD), which is associated with low levels of GH. Some potential symptoms may include increased sensitivity to temperature, higher body fat percentages, earlier muscle fatigue during exercise, decreased muscle mass, and mental health problems including depression and the feeling of loneliness. This shows the critical importance of balanced levels of IGF-1 in our bodies for our overall well-being. Just as those with Laron Syndrome, there are treatment options that can increase the amount of IGF-1 in the body which are accompanied by decreased risks for mental health and muscular deficiencies.
Relevance to Sports World
The role of IGF-1 is to function as a growth factor and as discussed earlier works alongside Growth Hormone. This relation to GH has brought criticism from the world of sports, in that this could be used as a performance enhancing drug. The relation between the two hormones has caused IGF-1 to be on the list of banned substances, just as GH is for most sports because of their similar role in muscle building. The central pathway for the regulation of muscle mass is P13K/AKT pathway, in which protein synthesis is activated and protein degradation is inhibited. This pathway is activated by exercise and is direct recipient of circulating IGF-1. As IGF-1 production is a GH-dependent event, this suggests that without GH or IGF-1 we would have little to no muscular growth. Those with GH deficiencies tend to have increased body fat and decreased fat-free mass, as well as decreased muscle strength and exercise tolerance, which is likely due to IGF-1 production also being down-regulated.
References
- ↑ Laron Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol Pathol. 2001 Oct;54(5):311-6. PMID:11577173
- ↑ Velloso CP. Regulation of muscle mass by growth hormone and IGF-I. Br J Pharmacol. 2008 Jun;154(3):557-68. doi: 10.1038/bjp.2008.153. PMID:18500379 doi:http://dx.doi.org/10.1038/bjp.2008.153
