IGF-1 DES Peptide: Research in Neuroprotection and Immunity Enhancement

by | Jul 14, 2023 | peptides

IGF-1 DES Peptide Research in Neuroprotection and Immunity Enhancement
IGF-1 DES, a splicing variant of insulin-like growth factor-1, appears to represent a truncated and naturally occurring form of the protein. It is considered to be endogenously present in the brain, breast milk, and uterine tissue. Research indicates that IGF-1 DES peptide may encompass the induction of hypertrophy and hyperplasia in various cellular lineages. Extensive investigations have indicated its possible superior potency when compared to the standard IGF-1, attributed to a possibly heightened bioavailability. 

Current scientific endeavors are aimed at exploring the potential of IGF-1 DES inflammation and neurological disorders. Notably, research indicates that IGF-1 DES may play a role in preserving the integrity of synaptic connections within the central nervous system. Moreover, akin to all forms of IGF-1, it appears to facilitate the regeneration of muscle and connective tissues, thereby potentially contributing to their repair and maintenance.

What is IGF-1 DES peptide?

IGF-1 DES is a truncated variant of IGF-1 that, according to the research studies, appears to lack the N-terminal tripeptide Gly-Pro-Glu, which is a naturally occurring form of the protein. In terms of cellular effects, IGF-1 DES appears to exhibit significantly higher potency compared to IGF-1, possibly as it appears to be unaffected by IGF-1 binding proteins. This characteristic is believed to render IGF-1 DES approximately ten times more potent than IGF-1 in inducing hypertrophy and cell proliferation.

IGF-1 DES has emerged as a subject of great importance in researching various neurological and neurodevelopmental disorders.(1) Investigations have suggested the potential influence of IGF-1 and its analogs on synaptic health in neurons. In animal models of autism, for example, both IGF-1 DES and IGF-1 appear to exhibit the ability to ameliorate symptoms and possibly improve various behavioral aspects associated with the condition.

How was the IGF-1 DES peptide discovered?

The discovery of insulin-like growth factors (IGFs) dates back to the 1950s, during which their initial function as regulators of sulfate intake was identified. Subsequently, independent studies unveiled their possible involvement in insulin activity, leading to their classification as “insulin-like growth factors”.(2) 

Over time, diverse mutations of IGFs were discovered and investigated through gene targeting techniques, aiming to enhance their bioavailability and potency.

One such mutation, known as IGF-1 DES, was initially isolated from bovine cells and subsequently identified in the brain and porcine uterus. Notably, these sources of IGF-1 DES appeared to exhibit superior potency compared to the regular IGF-1.(1)

How does the IGF-1 DES peptide exert its potential effects?

IGF-1 hormone peptides are suggested to interact with IGF-1 receptors, which accounts for their classification as insulin-binding proteins. Recent studies(3) have shed light on the possible mechanisms underlying the actions of IGF-1 DES in the body, revealing the following pathways:

Stimulation of CA1 fEPSPs (Excitatory Post Synaptic Potentials):

The activation of IGF-1 DES appears to lead to the influx of positively charged ions into the cell, potentially resulting in the generation of excitatory post synaptic potentials. Notably, in experimental studies where IGF-1 DES was introduced for a duration of 15 minutes, a substantial 40% increase in the slope of CA1 fEPSPs was reportedly observed. These findings suggest that the peptide may exert its function by directly interacting with and stimulating ion channels.

Involvement of a PI3K-dependent mechanism:

In an effort to elucidate the excitatory transmission exerted by IGF-1 DES in the CA1 region, an experiment(3) was conducted, wherein brain cells were introduced with IGF-1 DES along with either tyrosine kinase inhibitor or PI3K inhibitor compounds. Both tyrosine kinase and PI3K are enzymes that appear to be involved in crucial cellular processes, including cell growth, differentiation, proliferation, and even cancer prognosis.

Interestingly, the introduction of tyrosine kinase inhibitors did not appear to impede the functioning of IGF-1 DES. However, when PI3K inhibitor compounds were employed, a reduction was apparently observed in the fEPSP slope.

These experimental findings indicate that IGF-1 DES may stimulate excitatory synaptic transmission in brain cells, possibly primarily mediated through the PI3K pathway.

 

Research Studies on IGF-1 DES Peptide

IGF-1 DES Peptide and Neuroprotection Activities

IGF-1 DES peptide appears to exert significant influence on synaptic formation, possibly playing a role in essential cognitive functions like learning and memory. Research indicates that IGF-1 may particularly be involved in the development and maintenance of mature synapses. Research indicates that proper levels of the presynaptic protein synapsin-1, which regulates neurotransmitter release, might depend on IGF-1. Furthermore, IGF-1 appears to be involved in the post-synaptic protein PSD-95, that appears to be responsible for maintaining synaptic structure. 

IGF-1 and its analogs have shown positive action in conditions such as Rett syndrome and chromosome 22-deletion syndrome. As per researchers, “has been demonstrated to reverse the reduction in the number of excitatory synapses and the density of neurons that characterize these conditions in animal studies, and it is being introduced as an experimental treatment.”(4)

Clinical trials investigating IGF-1 in multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD) appear to yield varying outcomes. ALS test subjects in IGF-1 studies appeared to exhibit significant reductions in disease progression, potential muscle strength improvement, and probable enhanced respiratory function. However, the action of IGF-1 on MS appeared to be minimal, likely due to the nature of the condition, which involves damage to cells surrounding neurons rather than neuron death. Clinical trials for IGF-1 in PD are yet to be conducted, but rat models have suggested its possible potential in protecting dopaminergic neurons and improving behavior.(5)

IGF-1 DES Peptide and Autism Research

Scientific data highlights the potential significance of IGF-1 in various neurological conditions, including autism. Notably, younger individuals with autism appear to exhibit lower levels of brain-derived IGF-1 compared to age-matched individuals without the condition. This observation suggests that decreased concentrations of IGF-1 in the brain, particularly during early developmental stages, might disrupt normal neurodevelopment and contribute to the pathogenesis of autism, as “the action of IGF-1 is (reportedly) most pronounced in the developing brain”.(6)

An experimental study on mouse models indicated that IGF-1 DES introduction for a brief period of five days resulted in possible improvements in social interaction, novel-object recognition, contextual fear conditioning, reduction in repetitive/compulsive behavior, enhanced grooming, and enhanced memory capacity in these mice.(7)

These findings are not surprising, considering that autism is believed to arise from disturbances in synapse development. Pathologically, autism shares similarities with other neurodevelopmental conditions like fragile X syndrome, tuberous sclerosis, and Angelman syndrome.(8)

IGF-1 DES Peptide and Cognitive Function

In the brain, IGF-1 appears to undergo significant modifications, possibly forming shortened forms, indicating that analogs like IGF-1 DES may possess greater potency than the intact IGF-1 molecule. These modified molecules, including IGF-1 DES, appear to exhibit enhanced ability to cross the blood-brain barrier, possibly making them more impactful. Both IGF-1 and its analogs have been speculated by researchers to host the potential ability to mitigate neuronal death and possibly provide neuroprotection against neurodegenerative conditions.(8)

Furthermore, studies in rats suggest that IGF-1 DES might enhance synaptic transmission and possibly confer positive cognitive impact. This could be possibly advantageous for learning and memory processes, especially as organisms age and experience a decline in endogenous levels of IGF-1 within the brain. Research indicates that IGF-1 DES may induce a significant 40% increase in excitatory post-synaptic potentials.(9)

IGF-1 DES Peptide and Wound Repair

Dermal fibroblasts appear to play a critical role in tissue repair processes following injury. Interestingly, these cells have been suggested to produce various insulin-like growth factor binding proteins (IGFBPs) under specific conditions. Notably, IGFBPs appear to significantly reduce the impact of IGF-1 on its other receptors. Research indicates that the levels of IGFBPs may be influenced by inflammatory cytokines, which may potentially affect the healing process. However, by presenting peptides that are not affected by IGFBPs, it may be possible to bypass the effects of inflammatory cytokines and possibly enhance fibroblast growth and differentiation. Consequently, this modulation might lead to an accelerated wound healing response.(10)

IGF-1 DES Peptide and Immunity

Various immune cells, including mononuclear cells and neutrophils, appear to express IGF-1 receptors on their surface. Recent research suggests that IGF-1 DES may enhance immune function through distinct mechanisms. It has been hypothesized that IGF-1 DES may possibly promote the release of hydrogen peroxide in mononuclear cells, which may play a role in immune defense. Additionally, the peptide also appears to stimulate neutrophils to undergo differentiation into blastocytes, which are the specialized cells reportedly involved in eliminating pathogens.(11)

IGF-1 DES appears to exhibit greater potency in inducing these immune responses compared to IGF-1. That said, investigations into the role of IGF-1 DES in immune stimulation are still in the early stages, and research in this area is ongoing.

IGF-1 DES Peptide and Cancer

A significant challenge posed by cancer cells is their undifferentiated state or their presence at early stages of differentiation. This characteristic appears to render these cells resistant to elimination and compromises their functionality. Notably, cells in more advanced stages of differentiation appear to exhibit slower growth rates. The induction of differentiation in cancer cells may potentially decelerate tumor growth. Preliminary research conducted in cell culture has suggested that IGF-1 DES may possess the ability to promote differentiation in specific types of cancer cells, thereby possibly impeding tumor growth through differentiation inhibition.(12)

 

Synopsis

IGF-1 DES is a peptide that research indicates may exhibit greater potency when compared to IGF-1 due to its structural modifications. The peptide appears to act through multiple mechanisms, including stimulation of hypertrophy and hyperplasia of various cell lines, as well as possible promotion of synaptic health in the central nervous system. Researchers report that it may exert its effects by possibly interacting with ion channels and modulating the PI3K pathway. Moreover, IGF-1 DES peptide appears to show potential in improving immune function, possible induction of differentiation in certain cancer cells, and possible enhanced wound healing through its impact on fibroblast growth and differentiation. Research continues to date to fully elucidate the working mechanism and impact of IGF-1 DES peptide.

 

References

  1. 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. doi: 10.1016/1357-2725(96)00056-8. PMID: 8930132. https://pubmed.ncbi.nlm.nih.gov/8930132/ 
  2. IGF-1 (Insulin-like Growth Factor 1) Test. https://medlineplus.gov/lab-tests/igf-1-insulin-like-growth-factor-1-test/ 
  3. 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 
  4. Canitano R. New experimental treatments for core social domain in autism spectrum disorders. Front Pediatr. 2014 Jun 20;2:61. doi: 10.3389/fped.2014.00061. PMID: 24999471; PMCID: PMC4064155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064155/ 
  5. Costales J, Kolevzon A. The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders. Neurosci Biobehav Rev. 2016 Apr;63:207-22. doi: 10.1016/j.neubiorev.2016.01.001. Epub 2016 Jan 15. PMID: 26780584; PMCID: PMC4790729. https://pubmed.ncbi.nlm.nih.gov/26780584/ 
  6. Riikonen R. Insulin-Like Growth Factors in the Pathogenesis of Neurological Diseases in Children. Int J Mol Sci. 2017 Sep 26;18(10):2056. doi: 10.3390/ijms18102056. PMID: 28954393; PMCID: PMC5666738. https://pubmed.ncbi.nlm.nih.gov/28954393/ 
  7. 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, 38 (4) 1015-1029; DOI: https://doi.org/10.1523/JNEUROSCI.2010-17.2017 
  8. 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/ 
  9. 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. doi: 10.1016/j.neuint.2007.04.030. Epub 2007 May 16. PMID: 17582656. https://pubmed.ncbi.nlm.nih.gov/17582656/ 
  10. Yateman ME, Claffey DC, Cwyfan Hughes SC, Frost VJ, Wass JA, Holly JM. Cytokines modulate the sensitivity of human fibroblasts to stimulation with insulin-like growth factor-I (IGF-I) by altering endogenous IGF-binding protein production. J Endocrinol. 1993 Apr;137(1):151-9. doi: 10.1677/joe.0.1370151. PMID: 7684061. https://pubmed.ncbi.nlm.nih.gov/7684061/ 
  11. 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/
  12. 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/