IGF-1 DES Description
IGF-1 DES (Insulin Growth Factor – 1 DES) is a single, non glycosylated polypeptide chain that is made up of 67 amino acids. It is the shorter version of the IGF-1 amino acid chain that contains amino acids 4-70 and as such it mimics the insulin structure. This polypeptide omits the first three amino acids at the N-terminus of IGF-1 and this omission considerably lowers its binding to the IGFBPs (insulin-like growth factor-binding proteins) and boosts its potency. Its structure has ensured that the properties of IGF-1 can be amplified with more stability. IGFs (somatomedins) are growth hormones that play a great role in growth and development. IGF-1 DES is also synthesized naturally in the human body and its physiological role is to positively impact protein synthesis, RNA synthesis, transportation of amino acids and glucose into the cells, and to lower protein catabolism. It is also believed to promote neurogenesis and functions. Its amino acid sequence is TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA and it has a molecular mass of 7372 Daltons. IGF-1 DES is also referred to as IGF-1 DES, IGF-1, IGF-1 DES 1-3, Somatomedin C analogue, Detropin. It has a half-life that ranges between 20-30 minutes (it is a very delicate amino acid chain) and its potency is 5 times that of IGF-1 LR3 and 10 times that of regular base IGF-1.
Product History
Initial studies had demonstrated that GH did not have direct stimulation effects on the incorporation of sulfate into cartilage, but somewhat acted via a serum factor. This serum factor was then referred to as ‘sulfate factor’ and with time was named ‘somatomedin’ or IGF-1 and recently it was truncated to DES IGF-1. In vitro experiments established that when administered at equal doses, IGF-1 DES has a potency of about 10 times that of IGF-1 at stimulating hypertrophy and proliferation in cell cultures. Due to its short half-life, IGF-1 DES should be administered directly to the site where muscle growth is desired.
Scientific Study
Research has shown that IGF-1 DES has a clearance rate from plasma that is about 4 times faster than that of IGF-1 but its metabolic effects are longer lasting than those of IGF-1 by about 3-5 times. This has been attributed to the fact that IGF-1 DES retains high concentrations after clearance in the extracellular space of targeted tissues compared to IGF-1. Studies have demonstrated that IGF-1 DES stimulates proliferation in cultured myoblasts. Despite binding to the same type I IGF receptor as IGF-1, IGF-1 DES has only 1% binding affinity to IGFBPs (IGF binding proteins) which has been shown to be excreted in almost all mammalian cells; as such, much lower quantity of IGF-1 DES offers biological activity offered by a higher IGF-1 dose. Animal based studies have shown that the key mechanical operation of IGF-1 DES is supported by its ability to create hyperplasia. Hyperplasia also referred to as hypergenesis is the process by which the proliferation and increase of cells is regulated and controlled.
In a variety of rat models (diabetic, normal adult, GH deficient, chronic renal failure, dexamethasone-treated, and partial gut removal), IGF-1 DES was shown to have a strong and consistently greater effect on body growth which ranged between 1-3 times. In rats, IGF-1 DES has been shown to affect growth in majority of the tissues, however, carcass fat tends to reduce and muscle weight tends to increase fairly less than body weight.
IGF-1 and GH (growth hormone) play a key role in the development and growth of tissues within the mammalian body. Research has shown that plasma IGF-1 concentrations tend to peak during puberty and then decline with age. In one particular study, researchers had determined that chronic treatments to reinstate plasma IGF-1 concentrations attenuated spatial learning deficits in aged rats. However, little information was available at the time on the effects of chronic actions of IGF-1 within the brain; as such, researchers performed a study in which they evaluated the acute effects of des IGF-1. They used hippocampal slices harvested from young Sprague-Dawley rats to distinguish the acute effects of des-IGF-1 on excitatory synaptic transmission in the CA1 region. They noted a 40% increase in FEPSP (field excitatory postsynaptic potential) slope after introduction of des-IGF-1 at 40 ng/ml. They then utilized whole cell patch-clamp recordings to establish whether this improvement was as a result of postsynaptic mechanism that involved AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate) and not N-methyl-D-aspartate receptors. However, the improvement was totally inhibited by gestistein, the broad spectrum tyrosine kinase inhibitor, and substantially lowered by the P13K blockers wortmannin, and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; this indicates that the effect was largely dependent on the activation of P13K. this differentiation in properties of IGF-1 DES within hippocampal excitatory synapses could offer insight on how long term increases in plasma IGF-1 affect cognitive benefits in aged rats. A rise in AMPA receptor-mediated synaptic transmission possibly contributes to cognitive enhancement or initiates long-term changes in the synthesis of proteins that play a key role in learning and memory such as brain-derived neurotrophic factor.
In vitro study was carried out to analyze the effects of IGF-1 DES, basic fibroblast growth factor, and brain-derived neurotrophic factor on morphological growth, survival, and transmitter-specific differentiation of the dopaminergic neurons in rats. Basic fibroblast growth factor, IGF-1 DES, and brain-derived neurotrophic factor were shown to differentially regulate development in dopaminergic cells. Administration of brain derived neurotrophic factor was observed to stimulate survival, dopamine uptake activity, and the formation of primary neuritis. IGF-1 DES had the highest potency in promoting survival, had lesser efficacy in stimulation of dopamine uptake compared to the brain derived neurotrophic factor, and did not change the morphology of dopaminergic cells. On the other hand, basic fibroblast growth factor was shown to stimulate relatively mild increases in dopamine uptake and survival, and demonstrated slight reduction in neurite growth of the cells. The three factors did not stimulate the expression of tyrosine hydroxylase gene. Based on the results from this study, the researchers concluded that effective growth factors have potential to stimulate varying, but partially overlapping, molecular pathways in the developmental differentiation stage; the three factors do not stimulate dopaminergic cell differentiation that can be contrasted with the pronounced trophic action of the nerve growth factor on basal forebrain cholinergic neurons or on peripheral sympathetic neurons; and the localization and effects of the three factors are not compatible with a role as target derived survival-regulating neurotrophic factor.
In vivo experiments were performed to evaluate the changes in the extent of the phosphorylation of Akt-1, ERKI/2 and p70 S6K in skeletal and cardiac muscles of mice after the animals had received DES-igf-1 by means of intraperitoneal injection. The researchers then measured the plasma levels of insulin, glucose, and IGF-1. In the observations, administration of des IGF-1 did not show any effects on plasma levels of IGF-1, or insulin, however, plasma levels of glucose had significantly dropped by approximately 50%. In skeletal and cardiac muscles, administration of des-IGF-1 was shown to significantly increase the phosphorylation of Akt-1 at Ser 473 without any alterations in the phosphorylation of p42 and p44 MAP kinases at Thr202/Tyr204. Phosphorylation of p70 S6K at Thr421/Ser424 was only observed to have a significant increase within skeletal muscle and not within cardiac muscle. At Ser 133, the phosphorylation of the nuclear transcription factor CREB did not have any significant changes in both skeletal and cardiac muscle. Des IGF-1 was only shown to significantly increase the phosphorylation of the transcription factor FKHR within cardiac muscle. Based on the study results, the researchers concluded that administration of des IGF-1 resulted in differential effects in regard to the activation of PI 3 kinase and MAP kinase pathways in skeletal and cardiac muscles of mice.
In a rat based study, researchers investigated the effects of IGF-1, IGF-2, and des-IGF-1 on neuronal loss following hypoxic-ischemic brain injury in adult rats. In this study, the researchers were seeking to determine the mode of action of IGF-1 and the potential role of IGFBPs. The researchers administered IGF-1, IGF-2, des-IGF-1 (an analogue of IGF-1 that has a low binding affinity for IGFBPs), and a combination of IGF-1 with IGF-2 into the lateral cerebral ventricle just after an HI injury and then compared their effects after two hours (post injection). The researchers used right artery litigation and 10-minute exposure to 6% O2 to induce a unilateral HI in adult rats. They then measure the degree of neuronal loss in the striatum, cortex, hippocampus, thalamus, and dentate gyrus after five days (post treatment). Researchers observed a significant reduction in neuronal loss in all regions when 20 micrograms of IGF-1 were administered centrally in a total of 17 subjects. On the other hand, there was no reduction in neuronal loss when 20 micrograms of IGF-2 were administered to 17 subjects, 20 micrograms of des-IGF-1 were administered to 17 subjects, and 2 micrograms of des-IGF-1 were administered to ten subjects. However, the researchers observed a tendency towards a decrease in neuronal loss when 150 micrograms of des-IGF-1 were administered to 20 subjects. Compared to the vehicle-treated group of animals, administration of IGF-2 as a solo dose was shown to significantly increase neuronal loss within the hippocampus and the dentate gyrus. In the group administered with a combined dose of IGF-2 and IGF-1, 30 micrograms of IGF-2 were shown to significantly inhibit the neuroprotective properties of 20 micrograms of IGF-1 in 18 study subjects and also lowered the buildup of [3H] IGF-1 within the injured hemisphere in 4 study subjects. Based on these study results, the researchers concluded that IGFBPs play a role in targeting the neuroprotective activities of IGF-1 and that IGF-2 may displace IGF-1 from IGFBPs resulting in the reduction in effects of IGF-1.