Receptor Grade IGF-1 LR3 Peptide and Cellular Anabolism

Receptor Grade IGF-1 LR3 peptide may be described as a modified version of the endogenously occurring insulin-like growth factor 1 (IGF-1) – the endogenous mediator of the anabolic potential of growth hormone (hGH). In order to produce IGF-1 LR3, scientists sought to modify IGF-1 by replacing the third amino acid with arginine and by adding an extra sequence of 13 amino acids to the N-terminus, thereby creating IGF-1 Long R3 (IGF-1 LR3). This modified peptide may exhibit better-supported stability and may be more potent than the original IGF-1.

The additional N-terminal sequence and amino acid substitution are believed to support its biological activity by potentially increasing its affinity for IGF receptors while reducing its binding to proteins that may deactivate it^(1). Furthermore, the term “Receptor Grade” refers to the higher purity of this research reagent when compared to alternatives such as Media Grade IGF-1 LR3. This higher purity may prove crucial for laboratory studies on cellular growth, IGF receptors, and IGF-binding proteins. Even small differences in quality may potentially impact outcomes in studies like these.

 

Research

Receptor Grade IGF-1 LR3 Peptide and IGF Receptors

Research by Bastian et al. suggests that, while normal, IGF-1 appears to bind readily to IGF-binding proteins. This is supported by the peptide’s association with a high molecular weight complex of around 150 kDa. With a molecular weight so high, IGF-1 LR3 may not bind to these proteins at all.⁽²⁾ This appears to be due to its modified structure and the fact that the peptide is predominantly thought of as a free peptide. As a result, clearance rates seem to differ between the two peptides.

IGF-1, when bound to IGFBPs, may be retained in research models for a longer period. On the other hand, IGF-1 LR3 lacks this association and appears to be cleared more rapidly. Relevant researchers have noted that the “metabolic clearance rate for LR3IGF-I was 11-fold higher than for IGF-I.” This suggests that the potential to avoid binding IGFBPs might contribute to a faster clearance for IGF-1 LR3 in research models.

Instances of faster clearance have also been confirmed by independent laboratory studies on living research models, such as by Mongongu et al.^(3). At the same time; it also increases the availability of the peptide as a free peptide, which may more readily interact with the anabolic IGF-1 receptors. Studies such as research by Elis et al. also suggest that modifications that reduce the peptide’s affinity for IGF-binding protein may support an increase in the amount of free, bioactive IGF-1 available at tissue sites.⁽⁴⁾ This alteration might support IGF1 receptor activation, leading to a more robust anabolic response in laboratory settings.

Receptor Grade IGF-1 LR3 Peptide and Cellular Yield

According to researchers such as Morris et al. IGF-1 LR3 may offer potential advantages for in vitro research by better-supporting cell viability and protein production compared to other common cell stimulants often exposed to research models in in laboratory settings.⁽⁵⁾ It is observed that when serum-free cell cultures were exposed to IGF-1 LR3, the cells appeared to maintain higher viability over extended production periods. Researchers report that the peptide exhibited “equivalent or better performance using two recombinant CHO cell lines.” For instance, cultures exposed to IGF-1 LR3 at concentrations above 0.05 μg/mL apparently maintained around 75–80% viability after 10 days. In contrast, those exposed to other cellular stimulants like insulin revealed lower viability, which in some cases displayed the potential to drop below 50%.

This better-supported viability may be associated with IGF-1 LR3’s potential for more immediate activation of the IGF-1 receptor, which is posited to be more abundant in these cells than insulin receptors. The study further posits that IGF-1 LR3 might induce different receptor conformational changes and cycling kinetics, which might contribute to prolonged signaling and sustained recombinant protein production. In production cultures, these differences may lead to higher protein yields, suggesting that extending the culture time may be more feasible when using IGF-1 LR3.

Receptor Grade IGF-1 LR3 Peptide and Cellular Hypertrophy

Studies by Thomas et al. in catabolic research models suggest that IGF-1 LR3 may be more anabolic than IGF-1 because it appears to bind poorly to IGF-binding proteins.⁽⁶⁾ This reduced binding may allow IGF-I LR3 to be transferred more rapidly to tissue sites, possibly resulting in higher local free concentrations. These increased concentrations might then potentially support protein synthesis while decreasing protein breakdown, as suggested by better-supported nitrogen retention and reduced 3-methylhistidine excretion in the text models. 3-methylhistidine is a marker posited to reflect muscular tissue protein breakdown. Consequently, Thomas et al. concluded that IGF-1 LR3 may have been “2.5-fold more potent than IGF-I at improving weight gain and nitrogen retention”.

Receptor Grade IGF-1 LR3 Peptide and Muscle Cell Damage

Research by Gehrig et al. suggests that IGF-I LR3 may reduce contraction-mediated injury in dystrophic skeletal muscle cells.⁽⁷⁾ Exposed muscle cells apparently exhibited a lower force deficit following lengthening contractions compared with control muscle cells. For example, in the extensor digitorum longus, the force deficit following stretches that reached 40% beyond optimal fiber length appeared to be reduced. Similarly, the soleus and diaphragm muscle cells seemed to display a diminished susceptibility to injury at stretches exceeding 30% and 10–30% of optimal fiber length, respectively. This potential is posited to occur independently of alterations in muscular tissue fatigue or oxidative metabolism, as indices such as citrate synthase activity remained unaffected by the peptide.

It is possible that bypassing the inhibitory actions of IGF-binding proteins with IGF-I LR3 may allow for better-supported activation of IGF signaling pathways that contribute to a reduction in contraction-induced damage. Another experiment by Hill et al. also suggested that IGF-I LR3 may preserve muscle cell mass by reducing proteolysis.⁽⁸⁾ In the investigation, plasma levels of 3-methylhistidine were observed to be approximately 20% lower in the peptide group of research models compared to controls. This reduction in 3-methylhistidine may indicate that the IGF-1 analog potentially exerts an anti-catabolic impact on muscle cells by diminishing protein degradation. Although the exact mechanisms remain to be fully elucidated, IGF-I LR3 may modulate the balance between protein synthesis and breakdown in a manner that favors conservation of muscular tissue mass.

You can find Receptor Grade IGF-1 LR3 Peptide for sale with 99% purity, on our website (available for research use only).

NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

 

References:

1. Thomas, James N., and Victor Fung. “Comparison of long R3 IGF-1 with insulin in the support of cell growth and recombinant protein expression in CHO cells.” Animal Cell Technology. Butterworth-Heinemann, 1994. 91-95.
2. Bastian SE, Walton PE, Wallace JC, Ballard FJ. Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I) and an analogue LR3IGF-I in pregnant rats. J Endocrinol. 1993 Aug;138(2):327-36. doi: 10.1677/joe.0.1380327. PMID: 7693845.
3. 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.
4. Elis S, Wu Y, Courtland HW, Cannata D, Sun H, Beth-On M, Liu C, Jasper H, Domené H, Karabatas L, Guida C, Basta-Pljakic J, Cardoso L, Rosen CJ, Frystyk J, Yakar S. Unbound (bioavailable) IGF1 enhances somatic growth. Dis Model Mech. 2011 Sep;4(5):649-58. doi: 10.1242/dmm.006775. Epub 2011 May 31. PMID: 21628395; PMCID: PMC3180229.
5. Morris AE, Schmid J. Effects of insulin and LongR(3) on serum-free Chinese hamster ovary cell cultures expressing two recombinant proteins. Biotechnol Prog. 2000 Sep-Oct;16(5):693-7. doi: 10.1021/bp0000914. PMID: 11027158.
6. Tomas FM, Knowles SE, Owens PC, Chandler CS, Francis GL, Read LC, Ballard FJ. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochem J. 1992 Feb 15;282 ( Pt 1)(Pt 1):91-7. doi: 10.1042/bj2820091. PMID: 1371669; PMCID: PMC1130894.
7. 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.
8. 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.