Benefits of IGF-1 LR3 Peptides in Tissue Growth

by | Dec 21, 2022 | Research

 
Scientists have created IGF-1 LR3 peptides by modifying the amino acid sequence of IGF-1. The new peptide has similar effects but higher potency and improved stability. The LR3 in the name describes the two modifications to the IGF-1 molecule.

Long R3 IGF-1, or IGF-1 LR3, is an analog of insulin-like growth factor 1 (IGF-1). IGF-1 is an anabolic peptide hormone naturally found in the human body. Primarily, it is a mediator of the anabolic effects of the human growth hormone (HGH).

HGH stimulates the production of IGF-1 in the liver and almost all other tissues in your body. The IGF-1 produced in the liver is released in the bloodstream and exerts anabolic effects on the whole body, while the IGF-1 produced in all other tissues acts locally to stimulate growth.

The first is R3 which describes the replacement of the 3rd amino acid in IGF-1 with arginine. Scientists ascribed an additional 13 amino acids to the N-terminus of the R3 IGF-1 molecule, turning it into Long R3 IGF-1.
IGF-1 LR3 is an experimental peptide with potent anabolic and mitogenic effects, and its potential uses are still under active investigation.

 

What is the intended use of IGF-1 LR3 peptides?

Scientists developed IGF-1 analogs such as IGF-1 LR3 primarily for in vitro experiments to stimulate cell growth. IGF-1 and its analogs are highly anabolic towards actively proliferating cells. They can speed up cell replication in most tissues, ultimately shortening the time required to create a cell culture and use it to conduct laboratory studies.

IGF-1 LR3 works by activating IGF-1 receptors in most human and animal cells. Activating these anabolic receptors increases protein synthesis and tissue growth. It is much more stable and effective than IGF-1 alone, which makes it particularly effective for speeding up cell growth and proliferation. 

One of the main advantages of IGF-1 LR3 over other IGF-1 analogs is its bioavailability. IGF-1 LR3 binds to a much lesser degree to IGF-1 proteins than other available analogs. Therefore, its affinity to the anabolic IGF-1 receptors is much higher, and animal studies show that continuous infusion with IGF-1 LR3 leads to a 2-fold higher anabolic effect than IGF-1. Researchers also noted that “LR3 IGF-I remained more potent than IGF-I in several of these effects even when the peptides were given by once-daily injection.[1]

The reduced affinity to IGF-1 binding proteins also results in a shorter half-life of IGF-1 LR3. Animal studies show that IGF-1 LR3 is eliminated within 4 hours of an intramuscular injection.[2] At the same time, it caused significantly higher weight gain and organ mass increase in the tested animals compared to IGF-1.

The metabolites of IGF-1 LR3 have a longer half-life and can remain detectable in test animals for up to 16 hours after injection. In comparison, a high percentage of the natural IGF-1 binds to IGF-1 binding proteins, which reduces its effectiveness and prolongs its half-life by up to 15 hours.[3]

 

Uses of the IGF-1 LR3 peptide

IGF-1 LR3 may reduce muscle and weight loss in conditions that cause muscle wasting. However, there is still no research about its effects on humans; our only evidence is from animal experiments.

According to one study in a mice model of muscular dystrophy, IGF-1 LR3 administration was highly effective in reducing contraction-mediated injury.[4] Contraction damage is a major contributing factor to the pathophysiology of muscular dystrophy, so minimizing it may prove to be a promising intervention.

Another animal trial by Hill et al. also revealed that an IGF-1 LR3 infusion for 8 hours has a protective effect against loss of muscle mass loss and muscle catabolism during periods of restricted energy intake and caloric deficit. The researchers reported that “Long(R3)-IGF-1 infusion tended to preserve whole-body and muscle protein in beef heifers on a low-quality diet.” The continuous infusion also led to significant suppression of the natural IGF-1 synthesis.[5]

One trial in guinea pigs also reported a significant increase in the organ weight of the animals after a 7-day infusion of IGF-1 LR3. The researchers note that the infusion most significantly enlarged the adrenals, gut, kidneys, and spleen.[6]

It is important to note that IGF-1 LR3 and all other IGF-1 analogs mediate only the anabolic effects of HGH. All animal studies show these peptides have no catabolic, weight loss, or fat-burning properties.

 

Potential side effects of the IGF-1 LR3 peptide

There needs to be more research available on the side effects of IGF-1 LR3 to identify its side effects accurately. However, adverse reactions are likely similar to those observed with IGF-1-containing medications.

The main side effect of IGF-1 and its analogs are low blood sugar and hypoglycemia. The condition manifests with hunger, confusion, sweating, shaking, and dizziness. It may also lead to loss of consciousness in severe cases.

Hypoglycemia occurs when IGF-1 analogs, such as IGF-1 LR3, trigger both IGF-1 receptors and insulin receptors.[7] Activating the latter leads to an increased glucose uptake inside the cells, which leads to a rapid drop in blood glucose levels.

Another potential side effect is that IGF-1 LR3 can lead to the overgrowth of mucosal cells inside the intestines of animals. Research shows that the peptide can cause an increase in the number of mucosal cells in the small intestine, which can lead to aesthetic problems such as a bulging midsection.[8]

Unfortunately, IGF-1 LR3 may also suppress the natural IGF-1 production in the body, as this effect has been observed in experimental animals.[9] This is due to the negative feedback of high IGF-1 LR3 levels toward HGH synthesis.

IGF-1 LR3 may also have other potential side effects, such as stimulating the growth of existing tumors, acromegaly, and organ enlargement. Just like IGF-1, IGF-1 LR3 is also not likely to cause any of the other side effects typical for HGH, such as insulin resistance or water retention.[10]

 

References


  1. Tomas FM, Lemmey AB, Read LC, Ballard FJ. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. J Endocrinol. 1996 Jul;150(1):77-84. DOI: 10.1677/joe.0.1500077. PMID: 8708565.
  2. Mongongu C, Coudoré F, Domergue V, Ericsson M, Buisson C, Marchand A. Detection of LongR3 -IGF-I, Des(1-3)-IGF-I, and R3 -IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes. Drug Test Anal. 2021 Jul;13(7):1256-1269. DOI: 10.1002/dta.3016. Epub 2021 Feb 22. PMID: 33587816.
  3. Guler HP, Zapf J, Schmid C, Froesch ER. Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. Acta Endocrinol (Copenh). 1989 Dec;121(6):753-8. doi: 10.1530/acta.0.1210753. PMID: 2558477.
  4. Gehrig SM, Ryall JG, Schertzer JD, Lynch GS. Insulin-like growth factor-I analogue protects muscles of dystrophic MDX mice from contraction-mediated damage. Exp Physiol. 2008 Nov;93(11):1190-8. Doi: 10.1113/expphysiol.2008.042838. Epub 2008 Jun 20. PMID: 18567600.
  5. Hill RA, Hunter RA, Lindsay DB, Owens PC. Action of long(R3)-insulin-like growth factor-1 on protein metabolism in beef heifers. Domest Anim Endocrinol. 1999 May;16(4):219-29. doi: 10.1016/s0739-7240(99)00015-6. PMID: 10370861.
  6. Conlon MA, Tomas FM, Owens PC, Wallace JC, Howarth GS, Ballard FJ. Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig. J Endocrinol. 1995 Aug;146(2):247-53. DOI: 10.1677/joe.0.1460247. PMID: 7561636.
  7. Kovacs GT, Worgall S, Schwalbach P, Steichele T, Mehls O, Rosivall L. Hypoglycemic effects of insulin-like growth factor-1 in experimental uremia: can concomitant growth hormone administration prevent this effect? Horm Res. 1999;51(4):193-200. doi: 10.1159/000023357. PMID: 10474022.
  8. MacDonald RS. The role of insulin-like growth factors in small intestinal cell growth and development. Horm Metab Res. 1999 Feb-Mar;31(2-3):103-13. DOI: 10.1055/s-2007-978706. PMID: 10226789.
  9. Dunaiski V, Dunshea FR, Walton PE, Goddard C. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs. J Endocrinol. 1997 Dec;155(3):559-65. DOI: 10.1677/joe.0.1550559. PMID: 9488001.
  10. Martha S, Pantam N, Thungathurthi S, Rao VL, Devarakonda K. Study of insulin resistance in relation to serum IGF-I levels in subjects with different degrees of glucose tolerance. Int J Diabetes Dev Ctries. 2008 Apr;28(2):54-9. DOI: 10.4103/0973-3930.43100. PMID: 19902049; PMCID: PMC2772007.

Disclaimer: The products mentioned are not for human or animal consumption. All the information shared in this article is for educational purposes only.