What is lGF-1 DES?
IGF-1 DES is a truncated version of lGF-1 in which the tripeptide Gly-Pro-Glu is absentfrom the N-terminus end of the protein. lt is actually a naturally occurring variant of lGF-1and has been found in the human brain, cow colostrum, and pig uterine tissue.IGF-1DES is 10 times more potent than lGF-1 in stimulating hypertrophy and proliferation ofcells because it is not affected by lGF-1 binding proteins and therefore is morebioavailable. There is interest in using the peptide to induce anabolism in catabolicconditions (e.g. chronic illness) and in the treatment of inflammatory bowel diseasel1, p11.
IGF-1 DES has also been of keen interest in the treatment of a number of neurologicaand neurodevelopmental conditions. Researchers investigating autism and autismspectrum disorders have found that lGF-1 and its analogues have potent effects on thesynaptic health neurons. In animal models of autism, IGF-1 DES and lGF-1 have relievedsymptoms and improved a number of the behavioral aspects of the condition.
IGF-1 DESStructure
Sequence:
TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKAAKSA
Molecular Formula: C:1gH4sN,1O,SMolecular Weight: 7365.4225 g/mol
PubChem ClD: 135331146
CAS Number: 112603-35-7
Synonyms: Insulin-ike growth factor 1,des-(1-3)-, Des(1-3) 1GF-1,4-70-insulin-likegrowth factor 1
IGF-1 DESResearch
IGF-1 DES Is More Potent Than IGF-1
IGF-1 DES is lacking just three amino acids from its N-terminal end, but that subtlechange makes a big difference. Research shows that IGF-1 DES does not bind very welto lGF-1 binding proteins (lGFBPs) found in the blood and in various tissues throughoutthe body. The result is that more of the peptide is available for binding to importantreceptors and thus lGF-1 DES is more potent (same effects at lower doses) than lGF-1itself. Research in pigs and marmoset’s indicates that lGF-1 DES is 2-3 times morepotent than IGF-1 in lowering blood sugar. Further, these same potency effects extend toother properties of lGF-1 as well, including its anabolic effects on skeletal muscle and itsneuroprotective effects[2]
One of the benefits of binding to lGFBPs is prolonged activity as a result of decreasedclearance from the circulation. Thus, IGF-1 DES has a much faster onset of action, highelpeak activity, and faster withdrawal than lGF-1 itself. There are a number of settings inwhich this type of efficacy profile could be useful, including the treatment ofhyperglycemic conditions.
Research in pigs indicates that lGF-1 variants with low affinities for lGFBPs have a moredramatic effect on growth. In fact, the anabolic effects of IGF-1 DES occur even in thesetting of limited calorie intake[3]. Research in rats shows that just 14 days of IGF-1 DESis enough to produce significant increases in body weight, nitrogen retention, and foodconversion efficiency[4]. The latter fact is important as it confirms the potential of lGF-1DES to improve anabolism even in the setting of poor calorie intake, a function that wouldmake the peptide useful in chronic disease and in individuals who are unable to consumea great deal of calories for a variety of reasons. lGF-1 has also been shown to be a moreeffective anti-hyperglycemic agent, lower blood sugar rapid after administration. This ispart of the reason the peptide is so efficient in boosting growth with lower calorieconsumption. There is interest among researchers in using lGF-1 DES as a potentialtreatment in hyperglycemia were it would have similar effects to insulin administrationwithout the long-term side effects that can occur if too much insulin is used.
IGF-1 DES Research and Neurological Disease
It has been long established that IGF-1 has important effects on neuron growth,differentiation, and survival. The protein is a major factor in synaptic formation and thusplays a critical role in learning, memory, and more. lGF-1 is particularly important for thedevelopment and maintenance of mature synapses. Research shows that lGF-1 isabsolutely necessary for achieving proper levels of pres-synaptic synapsin-1, a proteinthat regulates the release of neurotransmitters. The peptide is also important for the postsynaptic PSD-95 protein, which maintains synaptic structure. Without lGF-1, synapticdevelopment is disrupted and deficits in motor skills, behavior, cognitive functioning, andlanguage all develop.
IGF-1 and its analogues have been tested in Rett syndrome and in chromosome 22deletion syndrome. In both cases, the peptides yield positive benefits. By protecting thenumber of excitatory synapses in the brain and by preserving neuron density. lGF-1 hasalso been shown to reduce the toxic effects of NDMA over-stimulation, thereby protectincneurons from excitotoxity, which can lead to neuron death. The benefits were so great inanimal studies that lGF-1 and its analogues are being introduced as experimentaltreatments in humans suffering from these devastating conditions5].
Clinical trials of lGF-1 in multiple sclerosis (MS), ALS, Parkinson’s disease (PD), andAlzheimer’s disease (AD) have yielded mixed results. In ALS, for instance, IGF-1treatment lead to significant reductions in disease progression, increased musclestrength, improved respiratory functioning, and increased quality of life. in MS, thepeptide had almost no effect. Human trials of lGF-1 in PD have not yet been performed.but studies in rat models of PD indicate that it protects dopaminergic neurons andimproves behaviorfs. Further study is required to understand the causes of theseconditions and how IGF-1 DES plays a role in their treatment. The fact that the peptidehas no impact on MS is not surprising as the condition is less caused by neuron deaththan by damage to the cells around neurons. lGF-1 DES and other lGF-1 analogues canhelp scientists to explore the basic pathophysiology of these conditions in order to betterunder their causes and thus develop potential treatments.
IGF-1 DES and Autism
Research shows that lGF-1 may be an important constituent in a number of neurologicalconditions, including autism. In fact, children with autism show lower brain levels of IGF-1than age-matched controls, suggesting that low IGF-1 concentrations in the brain,particularly at an early age, may disrupt normal development and be important in thepathogenesis of autism[7].
Research in mouse models of autism indicate that lGF-l and analogues like IGF-1 DESreverse all deficits associated with the conditions. Mice administered lGF-ll for just fivedays showed improved social interaction, better novel-obiect recoanition, enhancedcontextual fear conditioning, reduced repetitive/compulsive behavior, better grooming.and more. The mice even showed improve memory[8].
These findings should not come as any surprise as research suggests that autism is likelycaused by disruptions in synapse development and is similar pathologically, to otherneurodevelopmental conditions like fragile X syndrome, tuberous sclerosis, andAngelman syndrome. lGF-1 and its analogues, which have potent effects on synapsesare therefore ideal candidates for exploring various treatment strategies in thesedisorders[9].
IGF-1 DES May Have Cognitive Benefits in Age
IGF-1 is important in adults as well as children. in adults, the peptide is actually heavilymodified in the brain to make it shorter, indicating that analogues like lGF-1 DES mayhave better therapeutic potential than intact lGF-1. Molecules like lGF-1 DES alsopenetrate the blood-brain barrier more readily, making them more effective whenadministered exogenously. In adults, lGF-1 and its analogues have been shown to reduceneuronal death and protect neurons against insults like stroke, Alzheimer’s disease,Parkinson’s disease, and more[1o]
From the above, it is clear that lGF-1 and its analogues are useful in the setting ofneurological disease. Research in rats, however, suggests that IGF-1 DES may enhancesynaptic transmission and impart cognitive benefits even in normal rats. This could be ofbenefit to learning and memory, particularly as organisms age and natural levels of lGF-1in the brain begin to decline. According to research, IGF-1 DES causes a 40% increase inexcitatory post-synaptic potential[11] This suggests that the peptide could have profoundeffects on cognitive function, particularly in age-related synaptic dysfunction.
IGF-1 DES Research and lmmune Function
Many cells in the immune system, such as mononuclear cells and neutrophils, have lGF.1 receptors on their surface. Research shows that lGF-1 DES can improve immunefunction by boosting release of hydrogen peroxide in mononuclear cells and byencouraging neutrophils to differentiate into pathogen-killing blastocytes[12]. in all casesIGF-1 DES is more potent in stimulating these changes than lGF-1, indicating that thepeptide might be an effective adjuvant to antibiotics and other treatments used in thesetting of infectious disease. Research into the role of lGF-1 DES in stimulating immunefunction is very preliminary, but still very promising.
IGF-1 DES May lmprove Wound Healing
Dermal (skin) fibroblasts are the cell primarily responsible for tissue repair following injury.These cells turn out to produce a number of lGFBPs under certain circumstances and it isknown that this protein drastically lowers the impact of lGF-1 at its other receptors.Research suggests that inflammatory cytokines can alter lGFBP levels, which may impacthealing. By administering peptides that are unaffected by IGFBP, it is possible tocircumvent the effects of inflammatory cytokines and improve fibroblast growth anddifferentiation[13]. This, in turn, can accelerate wound healing.
GF-1 DES Research and Cancer
One of the problems that cancer cells present is the fact that they are undifferentiated orexist at very earlier stages of differentiation. This makes the cells difficult to treat and alsomakes them dysfunctional. Most importantly, cells in later stages of differentiation growmore slowly. Forcing cancer cells to differentiate could slower tumor growth. Research incell culture indicates that lGF-1 DES can force certain types of cancer cell to differentiatewhich slows tumor growth by inhibiting differentiation[14].
IGF-1 DES Is a New Contender
IGF-1 DES preserves many of the functions of lGF-1, such as enhanced skeletal musclegrowth and protection of neurons. lt is different, however, in that it does not bind toIGFBPs. This fact alone makes lGF-1 DES more useful in a number of ways, such asallowing the peptide to more easily pass into the brain when administered exogenously.IGF-1 DES hold a great deal of promise, which is why it is the subject of intense researchin fields that touch on neurodevelopment, stroke, cancer, wound healing, autism, andmore.
IGF-1 DES exhibits moderate side effects, low oral and excellent subcutaneousbioavailability in mice. Per kg dosage in mice does not scale to humans. IGF-1 DES forsale at PEPTIDE GURUS is limited to educational and scientific research only, not forhuman consumption. Only buy lGF-1 DES if you are a licensed researcher.
Article Author
The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan
holds a doctorate degree from Case Western Reserve University School of Medicine anda B.S. in molecular biology.
Scientific Journal Author
Dr. Clemmons’ clinical practice combines his interest in growth hormone and IGF-1withthe assessment of patients with hypopituitarism and patients with pituitary tumors thathypersecrete growth hormone or prolactin. Dr. Clemmons combines basic biomedicalresearch, clinical investigation and consultative endocrinology practice as well as clinicaleducation. His basic research involves understanding the molecular mechanisms bywhich insulin-like growth factors stimulate cellular proliferation and differentiation. Dr.Clemmons is also interested in how cells that are undergoing hyperglycemic stressrespond aberrantly to stimulation by these growth factors. Additionally, he is interested inthe mechanisms by which these factors stimulate differentiation particularly in osteoblastsand vascular cells. His clinical studies involve novel methods for reversing the effect ofthese factors in patients with diabetic nephropathy and retinopathy. In his clinical practicehe combines his interest in growth hormone and IGF-l with the assessment of patientswith hypopituitarism and patients with pituitary tumors that hypersecrete growth hormoneor prolactin. Chronology of experience: D: University of North Carolina, 1974; Intern andResident: Massachusetts General Hospital, Boston, MA, 1974-1976; Resident: JohnsHopkins, Baltimore, MD, 1976-1977; Fellowship Endocrinology: Massachusetts GeneralHospital, Boston, MA, 1977-1979; Assistant Professor of Medicine: University of NorthCarolina, 1979-1985: Associate Professor of Medicine: University of North Carolina.1985-1990; Professor of Medicine: University of North Carolina, 1990-1995; SarahGraham Kenan Distinguished Professor of Medicine: University of North Carolina, 1996.2019; Professor of Medicine: University of North Carolina, 2019-present.
Dr. Clemmons is being referenced as one of the leading scientists involved in theresearch and development of lGF-1 DES. In no way is this doctor/scientist endorsing oradvocating the purchase, sale, or use of this product for any reason. There is no affiliationor relationship, implied or otherwise, between PEPTIDE GURUS and this doctor. Thepurpose of citing the doctor is to acknowledge, recognize, and credit the exhaustiveresearch and development efforts conducted by the scientists studying this peptide. Dr.Clemmons is listed in [15] under the referenced citations.
Referenced Citations
1.F.J. Ballard, J.C.Wallace, G.L. Francis, L.C. Read, and F. M. Tomas, “Des(1-3)lGF-1: a truncated form of insulin-like growth factor-l,” Int. J. Biochem. Cell Biol..vol.28,no.10,pp.1085-1087,Oct. 1996.
2.F. M. Tomas, P. E. Walton, F. R. Dunshea, and F. J. Ballard,“GF-1 variants whichbind poorly to lGF-binding proteins show more potent and prolongedhypoglycaemic action than native lGF-1 in pigs and marmoset monkeys,” JEndocrinol., vol.155,no.2,pp.377-386, NOV.1997.
3.P. E. Walton, F. R. Dunshea, and F. J. Ballard, “In vivo actions of lGF analogueswith poor affinities for IGFBPs: metabolic and growth effects in pigs of differentages and GH responsiveness,” Prog. Growth Factor Res., vol.6, no.2-4, pp. 385-395,1995.
4.FJ.Ballard,P.E.Walton,S.Bastian,F.M.Tomas, J.C.Wallace, and G.L.Francis,“Effects of interactions between lGFBPs and lGFs on the plasmaclearance and in vivo biological activities of lGFs and IGF analogs,” Growth Regul..vol.3, no.1, pp.40-44, Mar. 1993.
5.R. Canitano, “New experimental treatments for core social domain in autismspectrum disorders,” Front. Pediatr., vol.2, p. 61,2014.
6.J. Costales and A. Kolevzon, “The Therapeutic Potential of insulin-Like GrowthFactor-1 in Central Nervous System Disorders,” Neurosci. Biobehav. Rev., vol. 63.pp.207-222,Apr.2016.
7.R.Riikonen,“Insulin-Like Growth Factors in the Pathogenesis of NeurologicalDiseases in Children,”Int.J.Mol. Sci., vol.18, no.10, Sep.2017.
8.A.B.Steinmetz,S.A.Stern,A.S.Kohtz,G.Descalzi, and C. . Alberini, “Insulin-Like Growth Factor ll Targets the mTOR Pathway to Reverse Autism-LikePhenotypes in Mice,”J.Neurosci.Off. J.Soc.Neurosci., vol. 38, no.4, pp.1015-1029,24 2018.
9.D. Ebrahimi-Fakhari and M. Sahin, “Autism and the synapse: emergingmechanisms and mechanism-based therapies,” Curr. Opin. Neurol., vol. 28, no. 2.pp.91-102,Apr. 2015.
10.D.C.Górecki, M.Beresewicz, and B. Zabtocka, “Neuroprotective effects of shortpeptides derived from the insulin-ike growth factor 1” Neurochem. Int., vol. 51, no8,pp.451-458,Dec.2007.
11.M.M.Ramsey, M.M.Adams, O. J.Ariwodola, W. E. Sonntag, and J. L. Weiner,“Functional characterization of des-IGF-1 action at excitatory synapses in the CA1region of rat hippocampus,”J.Neurophysiol., vol. 94, no.1, pp.247-254, Jul.2005.
12.X. Zhao, B. W. McBride, L. M. Trouten-Radford, and J. H. Burton, “Effects ofinsulin-like growth factor-l and its analogues on bovine hydrogen peroxide releaseby neutrophils and blastogenesis by mononuclear cells,” J. Endocrinol., vol. 139.no.2,pp.259-265,Nov. 1993.
13.M.E. Yateman, D.C. Claffey, S. C. Cwyfan Hughes, V. J. Frost, J. A. Wass, and J.M. Holly, “Cytokines modulate the sensitivity of human fibroblasts to stimulationwith insulin-like growth factor-l (IGF-1) by altering endogenous lGF-binding proteinproduction,”J.Endocrinol., vol.137,no.1, pp.151-159,Apr. 1993.
14.M.Remacle-Bonnet, F. Garrouste, F.el Atig, M. Roccabianca, J. Marvaldi, and GPommier, “des-(1-3)-lGF-1, an insulin-like growth factor analog used to mimic apotential lGF-ll autocrine loop, promotes the differentiation of human colon-carcinoma cells,”Int.J.Cancer, vol.52,no.6, pp.910-917,Dec.1992
15.J Clin Invest. 2004;113(1):25-27.https://doi.org/10.1172/JC120660.
