IGF-1 DES Peptide – A Highly Potent IGF-1 Variant
Insulin-like growth factor-1, commonly called IGF-1, is an endogenous hormone peptide that is vital to several anabolic bodily functions. IGF-1 promotes the synthesis of glycogen, synthesis of collagen, proliferation and differentiation of cells, and lysis mechanism induced by growth hormones (1).
Imbalances in IGF-1 concentrations may lead to severe biological dysfunctions including reduced growth rate, shorter body parts and lower weight, poor hair and nail growth – caused by decreased IGF-1 concentration; and obesity, excessive perspiration, skin alterations, and larger than usual facial features – caused by excessive IGF-1 levels (2).
It is important to maintain optimal levels of the hormone peptide in the body.
There are several different forms of IGF-1 synthesized in the body naturally, as well as developed artificially as medication, which either have the same or more potency as IGF-1 itself. One of the forms is called IGF-1 DES which is described in detail here.
What is IGF-1 DES?
IGF-1 DES is an identical peptide to IGF-1, truncated with the three amino acids absent from the N-terminus (3).
This absence of the tripeptide Gly-Pro-Glu is what makes IGF-1 DES 10 times more potent than IGF-1. Since the tripeptide is absent, IGF-1 DES cannot easily bind with the IGF-1 binding receptors, which results in higher proliferation and differentiation of tissue cells, thereby increasing biological effects (3).
IGFs were discovered during the 1950s, where their primary function was first identified as regulators of sulfate intake. Later on, during further independent studies, their role in insulin activity was discovered, hence giving it the name of ‘insulin like growth factors’ (4).
Various mutations of IGFs have since been discovered and studied through gene targeting approaches to elevate their bioavailability and potency.
IGF-1 DES was first isolated from the bovine cells, followed by the human brain and thereby the porcine uterus – all showing higher, better potential results than regular IGF-1 (3).
How Does IGF-1 DES Function?
IGF-1 hormone peptides bind with the IGF-1 receptors and exert their mode of actions. This is why they are also called the insulin binding proteins.
Studies (5) have shown that IGF-1 DES functions in the body through different routes as follows:
Stimulates CA1 fEPSPs (Excitatory Postsynaptic Potential)
The flow of the positively charged ions into the cell (thereby causing the excitatory post synaptic potential) results in the opening of various ion channels. Applying IGF-1 DES for 15 minutes resulted in a 40% slope increase of CA1 fEPSPs, suggesting that the peptide can exert its function by acting on and stimulating the ion channels.
Acts Via PI3K Dependent Mechanism
To better understand how the peptide exerts excitatory transmission in the CA1 region, an experiment (5) was carried out where the brain cells were treated with 40 ng/ml dose of IGF-1 DES and either with tyrosine inhibitor or PI3K inhibitor medications. Both tyrosine kinase and PI3K are enzymatic cells involved in cell growth, differentiation and proliferation, and thereby involved in cancer prognosis.
After use of these medications, it was observed that tyrosine kinase inhibitors did not interfere with IGF-1 DES functioning, however, PI3K inhibitor medications drastically reduced the fEPSP slope.
These experimental studies suggest that IGF-1 DES stimulates excitatory synaptic transmission in the brain cells in a dose dependent manner, mainly mediated through the PI3K pathway.
Advantages of Using IGF-1 DES
There are various benefits and uses of IGF-1 DES peptide including:
- Plays an important role in synaptic development including behavioral and cognitive functioning, language and motor skills
- Helps combat autism
- Potential to improve memory functions in aged people
- Improves wound healing
- Enhanced immune functioning
- Potential to fight certain carcinogenic cells
Research and Clinical Studies
One of the rare yet drastic genetic neurological ailments is called Phelan-McDermid syndrome (PMS). PMS is mainly characterized by developmental delays in patients, including speech delays, behavioral issues, and inability to perspire or feel pain. This is a genetic ailment primarily caused by deletion or mutation of the SHANK3 human gene (6).
A study (7) was conducted on the SHANK3 depleted mice who were administered with IGF-1 and its analogs via intraperitoneal route for two weeks. Daily administration for two weeks showed the reversal of several ‘unwanted’ bodily functions due to SHANK3 deficiency, including deficits in motor signaling and performance. This indicated that IGF-1 and its analogs have the potency to inhibit the development and progression of PMS syndrome.
Rett Syndrome is another one of the rare genetic disorders affecting brain development thereby leading to a loss of speech and motor skills. This ailment primarily occurs in girls, normally 6-18 months of age (8).
In another study (7), a mouse model induced with Rett Syndrome was administered with IGF-1 and its analogs. Treatment with IGF-1 analogs resulted in enhanced synaptic development and inhibition of phenotype defects, thereby reversing the effects of Rett Syndrome.
IGF1 DES Role in Autism Treatment
Autism spectrum disorder (9) is a rare genetic condition associated with poor brain development and inability of the patient to perceive and socialize with others due to poor communication and speech. ‘Spectrum’ term is mainly associated with this ailment due to its varying range of symptoms and intensity of the condition.
Research has shown that this ailment is probably caused by deficits in the synaptic development and is pathologically similar to other ailments such as tuberous sclerosis(10). Hence, it is no surprise that studies carried out with IGF-1 DES on the autistic experimental models yielded positive results.
A study (11) was conducted on autistic mouse models that were administered with IGF-II and its analogs, such as IGF-1 DES, at a dose of 30 microg/kg body weight. Within five days of administration, the peptide resulted in enhanced social interaction, improved understanding and behavioral skills, and reduced compulsive behavior. The cognitive functioning of the mice also improved significantly. This result indicated that IGF-1 DES shows potential in becoming a potent therapeutic agent in the treatment of autism in humans.
Role in Improved Cognitive Functioning
Research (12) has shown that IGF-1 peptide hormone is important in both children and adults for growth and development. While most of the peptides originate from the liver, there are some additional short peptide isoforms that are extremely potent as neuroprotective agents, and their mechanism does not solely depend on the IGF-1 receptors. These short isoforms, such as IGF-1 DES, can also easily cross the blood brain barrier and are highly stable. This suggests that these peptides are highly potent candidates for neuroprotective therapeutic actions in the medical field.
A study (13) was conducted on the hippocampal brain cells of the young rats to identify the effects of the IGF-1 DES peptide on the excitatory synapses of the brain region. Administration of 40 ng/ml IGF-1 DES resulted in a 40% increase in the excitatory synaptic responses primarily through AMPA receptors. This AMPA receptor mediated synaptic response suggests that IGF-1 DES may directly aid in improving the memory and learning function in young and aged rats.
Role in Boosting Immune Function
This study (14) was conducted to determine the effects of IGF-1 isoforms, namely IGF-1 DES and long R3 IGF-1, on immune function by acting on the mononuclear and neutrophil cells.
Cells were preincubated with a standard agent (no IGF-1), 12.5 microg/L dose of IGF-1 DES and 12.5 microg/L dose of long R3 IGF-1. As a result of this, there was higher hydrogen peroxide release from these cells by 65%, 64% and 32% respectively. At a dose of 100 microg/L IGF-1 DES was significantly more potent than long R3 IGF-1 in stimulating incorporation of thymidine compounds in the mononuclear cells.
These results suggest that IGF-1 DES is a potent peptide that can be used as an adjuvant to other treatments in combating various ailments associated with impaired immune functions. While this study was a very preliminary one on immune system improvement by IGF-1 DES, it delivered promising results for further consideration.
Role in Cancer Treatment
One of the primary issues with carcinogenic cells is that they remain undifferentiated or exist at very early stages of cell differentiation, making them difficult to treat and destroy. By differentiating these cancer cells, tumor development can be inhibited.
Research (15) has shown that when IGF-1 DES is administered in nanomolar amounts in the human carcinogenic HT29-D4 cells, it forces these cells to differentiate into a phenotype. Correspondingly, the early administration of IGF-1 DES can also impart moderate inhibition of cell proliferation of the HT29-D4 cells.
This suggests that IGF-1 DES may have the potency to differentiate certain types of cancer cells (in this case, colon carcinoma HT29-D4 cells) and thereby prevent tumor growth in the body.
Role in Growth Enhancement
A study (16) was conducted on post-surgical rats after removing approximately 80% of their gut jejunum and ileum muscles. Rats weighing 170g were administered with 0.96 and 2.5 mg/kg dose of IGF-1 and with 0.96 mg/kg dose of IGF-1 DES via osmotic infusions every day for seven days.
All the rats lost weight after surgery, however, 3 days after IGF-1 treatment, there was a significant weight increase, especially in the IGF-1 DES treated mice. The weight gain in the IGF-1 treated group was 14.7g whereas it was 21g in the IGF-1 DES treated mice. What’s more, the kidneys and thymus weighed much more after IGF-1 DES administration.
This result suggests that IGF-1 DES plays a much more potent role than IGF-1 in growth and development and has a promising tendency to be used as a therapeutic agent in treating human growth impairment.
In another study (17), the relative potencies of IGF-1 and IGF-1 DES were compared in small sized mice. Injections of the peptide were administered to these mice daily for 3 weeks. The doses included 30 micrograms of IGF-1, 3 micrograms and 30 micrograms of IGF-1 DES.
After three weeks, it was noted that mice treated with 30 micrograms of IGF-1 DES showed significant development in overall length and growth compared to other two doses. Also, the lower dose of IGF-1 DES, and not IGF-1, stimulated increase in kidney and heart weights. Higher doses of both IGF-1 and IGF-1 DES led to enhanced weights of liver and stomach muscles.
These results again demonstrate that IGF-1 DES is much more potent than IGF-1 in terms of growth and development.
IGF-1 DES Side Effects
Even though analogous to endogenous IGF-1, peptide IGF-1 DES imparts some side effects similar to that of IGF-1 therapy, considering their similarities in the biologic system.
These side effects include (1):
- Redness, inflammation, and numbness at the site of injection (most common)
- Joint ache
- Jaw pain
- Inflammation / swelling
Is It Banned From Sports?
Anabolic agents such as IGF-1 and their isoforms, including IGF-1 DES, have been misused by professional athletes in order to elevate their physical ability. These are called the ‘performance enhancing drugs (PEDs)’ which, based on various research data, have been misused by the athletes in the past to improve muscle mass and aesthetics.
This is the reason why IGF-1 and its variants have been included in the prohibited list of World Anti-Doping Association (1).
IGF-1 DES peptide is identical to naturally occurring IGF-1 peptide, with the only difference being the absence of the tripeptide in its N-terminus. This absence of the tripeptide causes reduced binding of the peptide to the IGF-1 receptors, leading to higher cell proliferation and increased effects. Various studies have been conducted showcasing the 10x potency of IGF-1 DES peptide in comparison to IGF-1.
IGF-1 DES mainly acts via the PI3K pathway inducing excitatory synaptic responses in the neurological system. This fact is primarily why IGF-1 DES has been studied to show its effects in potentially treating neurological disorders such as autism spectrum disorder and Rett syndrome, enhanced cellular growth and body development, combat cancer and improve the overall body immunity.
While IGF-1 has been approved by the US FDA, IGF-1 DES is yet to be clinically approved. Clinical trials are still ongoing to fully examine the effects of IGF-1 DES in humans and establish this peptide as a potent therapeutic agent.
1. Anderson, Lindsey J et al. “Use of growth hormone, IGF-I, and insulin for anabolic purpose: Pharmacological basis, methods of detection, and adverse effects.” Molecular and cellular endocrinology vol. 464 (2018): 65-74. doi:10.1016/j.mce.2017.06.010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723243/
2. IGF-1 (Insulin-like Growth Factor 1) Test. https://medlineplus.gov/lab-tests/igf-1-insulin-like-growth-factor-1-test/
3. Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM. Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Int J Biochem Cell Biol. 1996 Oct;28(10):1085-7. https://pubmed.ncbi.nlm.nih.gov/8930132/
4. Yakar, S et al., 40 YEARS OF IGF1: Insulin-like growth factors: actions on the skeleton (Jul 2018). Journal of Molecular Endocrinology, vol. 61 Issue 1. https://doi.org/10.1530/JME-17-0298
5. Melinda M. Ramsey et al, Functional Characterization of Des-IGF-1 Action at Excitatory Synapses in the CA1 Region of Rat Hippocampus, 01 Jul 2005. https://journals.physiology.org/doi/full/10.1152/jn.00768.2004
6. Phelan-McDermid Syndrome: Causes and Symptoms. https://www.massgeneral.org/children/phelan-mcdermid-syndrome
7. Canitano, Roberto. “New experimental treatments for core social domain in autism spectrum disorders.” Frontiers in pediatrics vol. 2 61. 20 Jun. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064155/
8. Rett Syndrome. https://www.mayoclinic.org/diseases-conditions/rett-syndrome/symptoms-causes/syc-20377227
9. Autism Spectrum Disorder. https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928
10. Ebrahimi-Fakhari D, Sahin M. Autism and the synapse: emerging mechanisms and mechanism-based therapies. Curr Opin Neurol. 2015 Apr;28(2):91-102. https://pubmed.ncbi.nlm.nih.gov/25695134/
11. Adam B. Steinmetz et al, Insulin-Like Growth Factor II Targets the mTOR Pathway to Reverse Autism-Like Phenotypes in Mice. Journal of Neuroscience. 24 January 2018. https://doi.org/10.1523/JNEUROSCI.2010-17.2017
12. Górecki DC, Beresewicz M, Zabłocka B. Neuroprotective effects of short peptides derived from the Insulin-like growth factor 1. Neurochem Int. 2007 Dec;51(8):451-8. https://pubmed.ncbi.nlm.nih.gov/17582656/
13. Ramsey MM, Adams MM, Ariwodola OJ, Sonntag WE, Weiner JL. Functional characterization of des-IGF-1 action at excitatory synapses in the CA1 region of rat hippocampus. J Neurophysiol. 2005 Jul;94(1):247-54. https://pubmed.ncbi.nlm.nih.gov/15985695/
14. Zhao X, McBride BW, Trouten-Radford LM, Burton JH. Effects of insulin-like growth factor-I and its analogues on bovine hydrogen peroxide release by neutrophils and blastogenesis by mononuclear cells. J Endocrinol. 1993 Nov;139(2):259-65. https://pubmed.ncbi.nlm.nih.gov/7508487/
15. Remacle-Bonnet M, Garrouste F, el Atiq F, Roccabianca M, Marvaldi J, Pommier G. des-(1-3)-IGF-I, an insulin-like growth factor analog used to mimic a potential IGF-II autocrine loop, promotes the differentiation of human colon-carcinoma cells. Int J Cancer. 1992 Dec 2;52(6):910-7. https://pubmed.ncbi.nlm.nih.gov/1281142/
16. Lemmey AB, Martin AA, Read LC, Tomas FM, Owens PC, Ballard FJ. IGF-I and the truncated analogue des-(1-3)IGF-I enhance growth in rats after gut resection. Am J Physiol. 1991 Feb;260(2 Pt 1):E213-9. https://pubmed.ncbi.nlm.nih.gov/1996625/
17. Gillespie C, Read LC, Bagley CJ, Ballard FJ. Enhanced potency of truncated insulin-like growth factor-I (des(1-3)IGF-I) relative to IGF-I in lit/lit mice. J Endocrinol. 1990 Dec;127(3):401-5. doi: 10.1677/joe.0.1270401. https://pubmed.ncbi.nlm.nih.gov/2280209/
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