Symptoms such as short stature or excessive growth gigantism may warrant a somatomedin C test. The test may also be used to assess a child's nutritional status, because malnutrition may reduce somatomedin C levels. Your child may be asked to stop eating and drinking for 10 to 12 hours before this test. On the day of the test, having your child wear a T-shirt or short-sleeved shirt can make things easier for your child and the technician who will be drawing the blood.
A health professional will clean the skin surface with antiseptic, and place an elastic band tourniquet around the upper arm to apply pressure and cause the vein to swell with blood. A needle is inserted into a vein usually in the arm inside of the elbow or on the back of the hand and blood is withdrawn and collected in a vial or syringe. After the procedure, the elastic band is removed. Once the blood has been collected, the needle is removed and the area is covered with cotton or a bandage to stop the bleeding.
Collecting blood for this test will only take a few minutes. Collecting a sample of blood is only temporarily uncomfortable and can feel like a quick pinprick. Afterward, there may be some mild bruising, which should go away in a few days. This was shown through administration of an antibody that blocked systemic IGF1 uptake into the brain parenchyma, which reversed the exercise-induced effects on hippocampal neurogenesis Trejo et al.
Exercise promotes functional recovery of spatial memory acquisition in rats who have undergone hippocampal injury, and attenuated the loss of motor coordination in rats following brainstem injury or Purkinje cell degeneration Carro et al. The neuroprotective effects of exercise demonstrated in this study were reduced in rats who received subcutaneous IGF1 antibody treatment Carro et al.
Memory deficits are frequently reported in depression, and imaging studies have shown decreased hippocampal volume in patients with depression. In addition to its role in neurogenesis in the adult brain, IGF1 has been studied for its effect on CNS reparation and plasticity using injury and sensory deprivation models. These studies may indicate that falling levels of IGF1 in the aging brain may indirectly lead to aging through reduced reparation, remodeling and resistance to stress.
One model of injury is the cerebellar deafferentiation model, whereby the olivocerebellar pathway is transected. The remaining olivocerebellar fibers reinnervate the hemicerebellum, but only in the early post-natal period days 7— However, injection of IGF1 into the cerebellum of rats aged 11—30 days allowed for reinnervation of this pathway, indicating that this period of neuroplasticity is extended with use of IGF1 Sherrard and Bower, IGF1-mediated reinnervation of the olivocerebellar pathway caused full motor recovery in rats rendered ataxic after 3-acetylpyridine-induced cerebellar injury Fernandez et al.
More evidence for its role in reparative neuroplasticity is shown through the use of excitotoxicity models. Chronic intracerebral administration of IGF1 following an excitotoxic lesion in the dentate gyrus caused increased dendritic formation in young neurons in the dentate gyrus compared to untreated controls, and recovery of contextual fear memory, which is a dentate gyrus-dependent function Liquitaya-Montiel et al.
Another model of dentate gyrus injury is injection of trimethyltin, which is shown to cause elevated IGF1 mRNA levels in the hippocampus.
IGF1 is also thought to be protective in hypoxic-ischemic injury. Intracerebroventricular infusion of IGF1 during perinatal asphyxia in near-term foetal sheep was linked to reduced loss of striatal cholinergic and GABAergic neurons compared to controls on post-mortem examination Guan et al.
A single dose of intracerebroventricular IGF1 2 h hypoxic-ischemic injury reduced somatosensory deficits for up to 20 days after the initial insult Guan et al.
The effects of malnourishment in the post-natal period are also attenuated by IGF1 administration. Malnourished mice treated with IGF1 comparable brain weights and cell numbers compared to nourished controls, and higher numbers of oligodendrocytes and expression of myelin markers MPB and PLP, suggesting that this protective effect is through increased myelination Ye et al. This was shown to be the result of post-traumatic proliferation and differentiation of neural stem cells into immature neurons, rather than through protection against initial insult.
IGF1 overexpression also enhanced dendritic arborization of immature neurons compared to normal controls Carlson et al.
Thus, through enhanced neurogenesis and maturation, IGF1 overexpression accelerated recovery. The role of IGF1 in activity-dependent neuroplasticity is also demonstrated through the use of sensory deprivation models. MD is a model of reduced activity-dependent activity, whereby one eye is deprived of visual stimuli, which leads to neuronal network reorganization with subsequent ocular dominance of the normal eye. Based on these findings, studies were performed to investigate whether administration of IGF1 in adult brains restores neuroplasticity.
Furthermore, in rats rendered amblyopic by long-term sensory deprivation, those treated with IGF1 prior to restoration of sensory input showed full recovery of visual acuity compared to rats untreated with IGF1 Maya-Vetencourt et al.
Downregulation of intracortical inhibitory GABA activity, increased utilization of glucose, and interaction with 5-HT were offered as potential mechanisms through which IGF1 mediates this restoration of plasticity. An alternative sensory deprivation model is that of hindlimb unloading HU. Administration of IGF1 prevents this change in somatotopic representation Papadakis et al.
These interventional studies have demonstrated that IGF1 administration alters neuronal plasticity in response to sensory deprivation in adult animals. The above studies outline the role of IGF1 in adult neurogenesis, reparation and reorganization in response to stressors.
It is therefore possible that loss of these IGF1-driven mechanisms with age leads to age-related cognitive changes. However, numerous studies outlined later in this article report the contrary theory that it is a reduction IGF1 signaling that is neuroprotective following CNS insult.
Pulsatile pituitary secretion of GH in response to stimuli such as induced hypoglycemia or arginine administration declines with age Laron et al. Numerous age-related changes in the brain have been identified that suggest changes in IGF1 signaling. The density of GH receptors decreases with age, while reports are conflicting regarding age-related changes in IGF1 receptor density, with one group reporting increased density of IGF1R expression in the CA3 region of the hippocampus Chung et al.
These findings would suggest that IGF1 signaling is reduced in the aging brain. How this is linked to functional changes in the aging brain is unclear. Therefore, studies have been done to examine whether reduced IGF1 signaling is linked to cognitive dysfunction.
Studies in humans found a significant correlation between better perceptual motor performance, information processing speed and fluid intelligence and higher circulating IGF1 levels Aleman et al. The MMSE is a well-validated test in terms of repeat-test reliability and tracking of cognitive function over time.
In a 2 year prospective study, higher levels of circulating IGF1 levels were associated with reduced cognitive decline over the study period. However, these findings are inconsistent, with many studies also reporting no correlation between IGF1 and attention, fluid intelligence, memory or cognitive decline Papadakis et al.
In any case, correlation does not imply causation. Therefore interventional studies in human were performed to assess if GH or IGF1 levels improved cognitive function, but the results were conflicting and ultimately inconclusive Papadakis et al. In mice, intracerebroventricular infusion of IGF1 attenuated age-related deficits in working and reference memory as assessed by Morris water maze and object recognition tasks Markowska et al.
Further work has been done in mice studies to assess the downstream molecular effects of IGF1 administration in an aging brain. Intracerebroventricular infusion of IGF1 has been shown to increase microvascular density in aged animals Sonntag et al. Local IGF1 increases local glucose utilization in the anterior cingulate cortex of aged rats Lynch et al.
Finally administration of IGF1 attenuates the age-related decline in neurogenesis in aged rats Lichtenwalder et al. In order to better understand the physiological roles of IGF1 in normal neurodevelopment and aging, one can look at IGF1 activity in the context of known disorders of neurodevelopment and neurodegeneration.
For instance, Rett Syndrome is an X-linked neurological disorder characterized by seemingly normal post-natal development initially, followed by a sudden deterioration in function, with loss of acquired functional and motor skills at 12—18 months of age. Rather than being a neurodegenerative process, the underlying pathology is thought to be a stagnation in neuronal maturation.
It is caused by a mutation in the MECP2 gene, which codes a transcriptional modulator. It is abundant in neuronal tissue and its expression correlates with that of synaptic maturation. Therefore, subcutaneous injections if IGF1 have been administered to both mouse models and human subjects to assess if this intervention can reverse the Rett Syndrome phenotype.
IGF1 has been shown to increase brain weight, dendritic spine density and levels of PSD, a post-synaptic scaffold protein that promotes synaptic maturation, in MECP2 null mice, as well as partially reverse the reduction in amplitude of excitatory post-synaptic current in MECP2 mice Tropea et al. Interestingly, persistence of ocular dominance plasticity following MD, a marker of neuronal immaturity, is a feature of MECP2 mouse models of Rett syndrome.
It is prevented by pre-treatment with IGF1, giving further evidence for the role of IGF1 in neuronal circuit maturation and reduction in neuroplasticity Tropea et al.
These studies indicate the role of IGF1 signaling in neuronal circuit maturation. Therefore, through the study of IGF1 in the context of disorders caused by poor brain development, it appears that IGF1 promotes neuronal development and brain maturation.
For a review focused on IGF1 function in neurodevelopmental disorders, see Vahdatpour et al. Findings through the study of IGF1 in age-related neurodegenerative disorders, however, have been contradictory, with some studies reporting that reduced IGF1 signaling is neuroprotective, while others claim that reduced IGF1 signaling with age contributes to brain aging. An AD mouse model with reduced IGF1 signaling was created, and was reported as having reduced neuronal loss and behavioral deficits compared to the control AD mouse model with normal levels of IGF1 signaling Cohen et al.
These mice also show greater resistance to oxidative stress than mice with intact IGF1 signaling Holzenberger et al. Similarly, another group demonstrated protection of the aging brain from amyloid pathology by knocking out neuronal IGF1R activity in the brains of adult rats Gontier et al.
In particular, hippocampal hypometabolism has been observed to correlate with faster progression to dementia Mosconi et al. AD could therefore represent a form of CNS insulin resistance. These AD neurons showed decreased intracellular levels of IRS1 and IRS2, in association with greater levels of the phosphorylated inactivated forms of these proteins. Similarly, another study showed that cerebral neurons in AD brains demonstrate reduced responses to insulin and IGF1 signaling, mainly through phosphorylation and subsequent inactivation of IRS1 Talbot et al.
Furthermore, IGF1R blockade in the choroid plexus worsens AD like pathology, causing amyloidosis, tau hyperphosphorylation and cognitive disturbance Carro et al. These studies would therefore suggest that decreased insulin-IGF1 signaling in the brain at least correlates with the development of AD. This is a triple repeat disorder caused by mutation of the HTT protein, whereby elongation of the CAG triple repeat leads to a resultant HTT protein with a prolonged polyglutamine tract.
This prolongated protein is cut into toxic fragments that aggregate, causing neurotoxicity and degeneration. Reduced IGF1 signaling is linked to pathological and symptomalogical improvements in mouse models of HD. This is attributed to fewer polyQ-HTT aggregates in the brain. Conversely, another study showed that treatment of neurons transfected with the HTT mutation with IGF1 reduced polyQ-htt aggregation through Akt-mediated huntingtin phosphorylation Humbert et al.
IGF1 signaling has many effects on metabolism, at the tissue and cellular levels. This signaling is not limited to glucose and lipid homeostasis but also influences protein turnover Sharples et al.
Manipulating IGF1 depends on our understanding of the metabolic trade-offs, especially in the brain, adipose tissue and skeletal muscle, that are associated with it. IGF and its related molecules are important in protein metabolism and the regulation of skeletal muscle mass.
The role of IGF1 and its related molecules in the maintenance of skeletal muscle mass in humans is especially important for elderly individuals whose IGF1 levels decrease with age and are at risk of frailty Maggio et al. Manipulating metabolism by using dietary restriction offers a similar mechanism to reduced IGF1 signaling in that it results in the inhibition of mTOR and it has also been linked to reduced IGF1 levels. It has the potential to be used in combination with an increase in protein or amino acid intake to counteract the losses in skeletal muscle that accompany a reduction in IGF1 Sharples et al.
Choosing which pathway to target poses an obstacle to the modification of IGF1 signaling. This, taken with the detrimental effects of KO on tissues such as skeletal muscle and the importance of IGF1 in metabolism in the developing brain, suggests that tissue-specific reductions in signaling may be one way of overcoming this obstacle.
In addition to approaches which take into account specific pathways and tissues, it may also be beneficial to investigate the differences in the effects of IGF1 reductions at different time points. Human population studies point to a positive impact of IGF1 reductions at a young age and elevations at an old age Sharples et al. It has been questioned whether the extended longevity afforded by reduced IGF-1 signaling and its effects on metabolism are mediated in the same way.
KO of IRS2 in the entire brain in mice does result in lifespan extension but at 22 months these mice are also overweight, hyperinsulinemic and glucose-intolerant, demonstrating the centrality of this pathway in metabolic homeostasis. Nutrient-sensing which is central to the regulation of glucose and lipid homeostasis is carried out by the leptin-sensitive neurons of the arcuate nucleus which contain IRS2 and the IR.
Interestingly, the decrease of IRS2 on leptin receptor-expressing neurons did not result in the increase in lifespan seen with overall IRS2 decrease. This provides a powerful starting point for the potential development of strategies to manipulate IGF1 function without causing metabolic dysfunction. The importance of IGF1 and its related molecules on metabolism is undeniable and if manipulated correctly could prove to be viable therapeutically. In conclusion, the above studies largely support a role for IGF1 signaling in brain development, and adult neuroplasticity and neurogenesis.
However, while numerous studies report that IGF1 signaling serves to delay brain aging, and that the known fall in IGF1 signaling with age acts as a causative factor in age-related brain changes, there remain as many studies that stand in contradiction, and suggest that a reduction in IGF1 signaling delays age-related changes and diseases.
IGF1 levels are higher in the developing brain, and this is shown, through the studies outlined above, to promote neuronal development. It activates the PI3K pathway, which promotes survival by directly inactivating pro-apoptopic machinery van der Heide et al. Post-natally, IGF1 promotes neuronal maturation, and has been shown to partially correct the phenotype of certain neurodevelopmental disorders.
IGF1 is associated, in the adult brain, with regions of continued neurogenesis. These findings would suggest that IGF1 signaling exerts an overall neuroprotective effect, and that falling IGF1 levels with age contribute to the effects of aging in the brain.
However, there also exists a body of evidence suggesting that reduced IGF1 signaling attenuates the effects of aging, both in the brain and in the whole organism. A reduction in IGF1 signaling increases the life span of C.
With regards to brain function, age-related decline in axonal regeneration in C. However, in the C. These findings would therefore suggest that the fall in IGF1 signaling with age is not in fact the cause of aging, but is perhaps a protective mechanism that occurs as to attenuate the effects of aging.
These contradictions may arise partly because of the differential activity of IGF1 signaling in the brain compared to the whole body in different experimental models. One particular study characterizes the distinction in Ames mice, which have a primary deficiency in GH, leading to low levels of circulating IGF1. These mice demonstrate a longer lifespan, which has been attributed to absence of GH-IGF1 signaling, thereby affording evidence that IGF1 signaling contributes to aging.
However, Sun et al. Furthermore, this correlated with higher levels of neurogenesis in the dentate gyrus, compared to the controls Sun et al. This elevated level of neurogenesis in the Ames mice may underlie the observation that these mice showed less age-related cognitive deficits.
Therefore, while globally reduced IGF1 signaling appears to extend the lifespan of these organisms, one should not assume that brain-specific IGF1 signaling is also reduced, or that the effect of IGF1 activity in the brain compared to the rest of the organism on the process of aging is necessarily the same. Contradictions again arise when studying the neuroprotective effect of IGF1 signaling in hypoxic-ischemic injury.
While above studies describe reduced neuronal loss following intracerebroventricular infusion of IGF1 see above , other studies report that following Cre-LoxP-mediated inactivation of IGF1R in forebrain neurons, there was reduced neuronal damage, inflammation and edema in response to hypoxic-ischemic insult De Maghalaes Filho et al.
In fact, the systems are highly regulated and the changes in each factor may have a different effect. Another factor to take into account is the integration insulin-IGF1 in the brain.
This interaction should be taken into account in therapies which use IGF1 to improve brain function, because the variability of the results may be due to different levels of insulin in the body. This theory is in line with the homeostatic function of IGF1 as a connector between body and brain. In addition, as demonstrated by Sun et al. Furthermore, it is possible that while IGF1 signaling continues to promote neuronal development and plasticity throughout life, through its effects on cellular apoptotic machinery, glucose utilization and other neurotrophic factors, such anabolic process may simultaneously contribute to aging through accumulation of reactive oxygen species and resultant prolonged oxidative stress over time.
In all, there remains much to be done in elucidating the role of IGF1 signaling in the brain as it develops, matures and ages. IGF1 appears to act in concert with BDNF and other neurotrophic factors to promote neurogenesis and remodeling in the brain. However, its overall effects on energy metabolism and cellular oxidation may contribute to aging in all organs. What is obvious is that it is not simply a matter of high IGF1 signaling early in life promoting development and falling levels thereafter underlying the process of aging.
An evolutionarily ancient pathway, IGF1 signaling has likely taken on numerous differential roles in different body tissues in health and disease Forbes, , and its complex effects on cellular maturation, tissue development and energy metabolism may contribute to organismal development and aging simultaneously.
SW wrote a consistent part of the manuscript. DA wrote part of the manuscript and contributed to the figures.
DT designed the structure of the review, wrote part of the manuscript and contributed to the figures. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Aberg, M. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. PubMed Abstract Google Scholar. IGF-1 has a direct proliferative effect in adult hippocampal progenitor cells.
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Brain Res. Apfeld, J. Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature , — Bach, M. Insulin-like growth factor 1 mRNA levels are developmentally regulated in specific regions of the rat brain. Barres, B. Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70, 31— Bartlett, W. Localisation of insulin-like growth factor-1 mRNA in murine central nervous system during post-natal development. Beck, K. IGF1 disruption results in reduced brain size, CNS hypomelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons.
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Autism When the needle pricks your arm or hand, you may feel a slight sting or pain. Afterward, the site may be sore. Malnutrition or not eating fasting will affect your results. You don't need to get ready for this test. Be sure your healthcare provider knows about all medicines, herbs, vitamins, and supplements you are taking.
This includes medicines that don't need a prescription and any illegal drugs you may use. Search Encyclopedia. Insulin-Like Growth Factor Does this test have other names? Why do I need this test? You may need this test if your healthcare provider believes that you have or are at risk for a GH-related disease, including: Acromegaly, or GH over-production. What other tests might I have along with this test?
You may also need these tests: X-rays to measure your bone age Thyroid function tests to rule out thyroid problems Other tests to check GH levels insulin-like growth factor binding protein-3, or IGFBP-3 Children may have clonidine, arginine, or glucagon blood tests.
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