What Is IGF-1 LR3?

 IGF-1 LR3, which stands for insulin-like growth factor-1 long arginine 3, is a member of the family of insulin-like growth factors (IGFs), which are potent growth factors in mammals. All IGF analogues share similarities in their amino acid sequences with the protein insulin. They have prominent roles in everything from physiologic growth to cell division and even cellular communication1 .

Insulin-Like Growth Factor 1 Function

IFG-1, which is made primarily by the liver, is produced in response to growth hormone. It plays critical roles in cell growth, programmed cell death (apoptosis), and cell division. In fact, IGF-1 actively encourages cells to divide while inhibiting apoptosis. The combined effect is maximal cell proliferation.IGF1R-43H,IGF1R

Though IGF-1 is associated with cell growth and division throughout most of the body, it has an opposite effect on adipose (fat) tissue. Individuals with IGF-1 deficiency tend to be obese, with underdeveloped muscle and skeletal tissue. A finding supported by recent research, which that IGF-1 levels are inversely correlated with body mass index (BMI)2 . IGF-1 is currently being investigated as a potential mechanism for countering the obesity epidemic as administration tends to burn fat and build muscle.

IGF-1 LR3

Because IGF-1 regulates cell division, there has been a push to develop synthetic analogues of the naturally occurring molecule. These analogues have the potential to be powerful anti-cancer agents, decrease obesity rates, and even treat chronic muscle diseases. Currently, the most potent IGF-1 analogue is IFG-1 LR3 (a.k.a. IGF-1-LR3, LR3-IGF-1, IGF-1 Long Arginine 3).

This peptide is identical to IGF-1 with the exception of a 13-amino-acid addition to the N-terminal end of the molecule and the conversion of the third glutamine residue to arginine. As a result of these changes, IGF-1 LR3 does not bind as strongly to IGF binding proteins (IGFBPs), which degrade naturally occurring IGF-1 and thus reduce its half-life and potency. As a result of the modifications discussed above, IGF-1 LR3 remains in the bloodstream for longer periods of time than IGF-1 and thus has a longer duration of action3 . IFG-1 has a half-life of about 15 minutes while its counterpart has a half-life closer to 30 hours (1 day).

Clinical Trials of IGF-1 and Its Derivatives

Several large-scale clinical trials have been conducted using IGF-1 and its analogues. The first of these studies investigated the use of the molecule in ALS (Lou Gehrig’s Disease) as well as Duchene Muscular Dystrophy (DMD). The DMD trial was carried out by the Children’s Hospital Medical Center in Cincinnati, Ohio. The study compared the effects of IGF-1 to those of corticosteroids. Results suggest that IGF-1 provides for better growth in boys with DMD without producing any serious neurological or cardiovascular side effects4 .

Additional clinical trials have studied the effects of IGF-1 in ALS, Rett syndrome, and autism. The results from the latter two trials are not yet available. IGF-1 provides no benefit in ALS, which isn’t surprising given the low dosage of the drug used and the fact that ALS is primarily a motorneuron disease and not a muscle-wasting disease. So, the question becomes where to buy IGF-1 LR3?

Resources

  1. Pollak, M. The Insulin Receptor/Insulin-Like Growth Factor Receptor Family as a Therapeutic Target in Oncology. Clin. Cancer Res.18, 40-50 (2012).
  1. Alderete, T. L. et al. Relationships Between IGF-1 and IGFBP-1 and Adiposity in Obese African-American and Latino Adolescents. Obesity19, 933-938 (2011).
  1. Laajoki, L., Francis, G., Wallace, J., Carver, J. & Keniry, M. Solution Structure and Backbone Dynamics of Long-[Arg 3 ]insulin-like Growth Factor-I*. J. Biol. Chem.275, 10009-10015 (2000).
  1. Rutter, M. M. et al. Growth hormone treatment in boys with Duchenne muscular dystrophy and glucocorticoid-induced growth failure. Neuromuscul. Disord. NMD22, 1046-1056 (2012).

ALL ABOUT PEPTIDES

Peptides are naturally occurring molecules that are smaller than proteins and which consist of two or more amino acids. They are considered to be short chains of amino acid monomers which are linked by peptide bonds. They are considered to be building blocks of proteins. There are several classes of peptides which depend on how they are produced. They are peptones, ribosomal peptides, non ribosomal peptides, milk peptides and peptide fragments. They can be referred by different names such as polypeptides, dipeptides and so on depending on the amount of amino acids contained in them.

Proteins are broken down into peptides through enzymatic action so as to make them work effectively in the body. They are easily used in the body since they do not need to be broken down due to their smaller size. They are considered to be more useful to the body due to their stable nature unlike amino acids which are considered to be very unstable. Peptides have different functions in the body such as regulating the various functions by directly interacting with respective cells. Some of them have immune activity while some are known to have hormone activity.

Some peptides act as cell communicating ingredients that control how cells react to diet and physical exercise. They are very important in wound healing and controlling the pathology of skin conditions such as eczema and dermatitis. When the skin’s collagen breaks down, specific peptides are formed which send signals to your skin to form new collagen to replace the damaged one. Peptides can also be applied topically to trigger the skin into forming new collagen even when it has not been broken down.

They are very common in the fitness world especially among athletes. They are also known to burn fat, build muscle and improve athletic performance. It achieves this by enabling the body to absorb more amino acids and make them easily available for the cells immediately after workout. It also helps to recover very quickly especially after an injury by encouraging of more muscle formation at a rapid rate and less fat formation during that process.

They have become the most common way of increasing muscle mass since they have an anabolic effect on the muscle mass of an athlete. They are also known not to have any side effects unlike steroids. Peptides are not easily detected in blood and urine samples unless a comprehensive test is carried out to detect it.…

What Is Melanotan 2?

Melanotan 2 (a.k.a. Melanotan II) is a synthetic (man-made) member of the melanocortin family of naturally occurring proteins. The melanocortins are hormones and signaling peptides critical to the production of melanin (pigment molecule and in the regulation of homeostatis, appetite, and sexual arousal. Melanocortins mediate their effects by binding to melanocortin receptors.

 The Effects of Melanocortins

Melanocortin (MC) receptors are found on cells throughout the body. Five different MC receptors, labeled (1) through (5), have been identified thus far. Understanding how those receptors work has allowed scientists to explore the effects of melanocortin and thus melanotan 2. Here are the effects of each MC receptor.

MC(1): MC(1) is found in melanocytes, skin cells that are responsible for the production of melanin, the pigment that imparts a dark color to the skin. It is also found on hair cells and is partially responsible, though not entirely responsible, for hair coloration.

MC(2): MC(2) is also called the adrenocorticotropic hormone receptor (ACTHR). It is found on the adrenal glands and controls the synthesis and secretion of adrenal hormones, such as the glucocorticoids. Excess stimulation of MC(2) can lead to Cushing’s syndrome. Most melanocortins do not bind to MC(2), but melanotan 2 is thought to have limited affinity.

MC(3): MC(3) plays roles in appetite control and homeostasis 1 . Unfortunately, the exact effects of MC(3) are not well understood at this point in time.

MC(4): MC(4) plays roles in feeding, sexual behavior, and male erectile function. Mutations in MC(4) have been linked to obesity2 .

MC(5): MC(5) appears to only effect exocrine glands (sweat glands and pancreatic islet cells).

The Effects

This peptide is thought to bind to MC(1), MC(2), and MC(4). Its interaction with MC(1) leads to skin darkening. Administration of melanotan 2 in test subjects has produced an average increase in tanning of about 50%. Research suggests that people could achieve the same level tanning without approximately half as much exposure to sunlight, which means less ultraviolet (UV) light exposure and thus safer tanning3 . Researchers are currently investigating whether melanotan 2 is beneficial in reducing rates of skin cancer or not.Melanotan 2

It is known to bind to MC(2), but the interaction is not thought to be substantial. Limited trials in laboratory settings have not demonstrated an increase in rates of Cushing’s disease when melanotan 2 is administered. It is still considered a hypothetical risk of the peptide.

There is a strong binding with MC(4), which makes it a potent treatment for erectile dysfunction. In fact, melanotan 2 is currently in phase I clinical trials, being investigated as a potential treatment for psychogenic erectile dysfunction4 . The erectile effects of melanotan 2 have been extensively investigated in rats 5,6 .

A final and as yet uncertain effect of melanotan II is on social anxiety. In particular, it has shown some promise in the treatment of autism. Thus far, tests have only been carried out in the prairie vole. Those tests have shown that melanotan II decreases the time required for a prairie vole to remember its lifelong companion and to resume mating7 .

Overview

Melanotan 2 is a synthetic melanocortin that binds to melanocortin receptors 1, 2, and 4. It has skin-darkening effects and is currently being investigated as a potential treatment for erectile dysfunction. It may or may not be useful as a treatment for social anxiety and autism.

Resources

 

  1. Meek, T. H. et al. Role of melanocortin signaling in neuroendocrine and metabolic actions of leptin in male rats with uncontrolled diabetes. Endocrinology155, 4157-4167 (2014).

 

  1. Xu, Y. et al. Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab.18, 860-870 (2013).

 

  1. Fitzgerald, L. M., Fryer, J. L., Dwyer, T. & Humphrey, S. M. Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in humans with MC1R variant alleles. Peptides27, 388-394 (2006).

 

  1. Wessells, H. et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J. Urol.160, 389-393 (1998). Checkout latest news and updates at http://www.theage.com.au/victoria/melanotan2-tanning-injections-promoted-as-safe-despite-serious-concerns-20150804-giqz0l.html

 

  1. Giuliano, F., Clément, P., Droupy, S., Alexandre, L. & Bernabé, J. Melanotan-II: Investigation of the inducer and facilitator effects on penile erection in anaesthetized rat. Neuroscience138, 293-301 (2006).

 

  1. Kimura, Y., Naitou, Y., Wanibuchi, F. & Yamaguchi, T. 5-HT(2C) receptor activation is a common mechanism on proerectile effects of apomorphine, oxytocin and melanotan-II in rats. Eur. J. Pharmacol.589, 157-162 (2008).

 

  1. Modi, M. E. et al. Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole. Neuropsychopharmacology40, 1856-1865 (2015).