IGF-II: The New Way To Get Swole

(ANSC 452 Assignment) Have you ever wondered: How are we going to feed the world? How do those little mice get such big muscles? Can we actually make animals more muscular? Well, here is part of the answer: IGF-II

1. Muscle Growth Promoter

Via builtreport.com

IGF-2 promotes proliferation of myoblasts which in turn leads to an increased amount of muscle fiber. These transgenic larger muscled animals, have a greater amount of IGF-2 expression compared to wild types . Therefore, increased amounts of IGF-2 are linked to an increased amount of muscle hyperplasia [5].

*Disclaimer- the image above is a myostatin knock out mouse*

2. How does this work?

Via clincancerres.aacrjournals.org

It has been seen that IGF-2 induces Pax3 in early stage embryos and MyoD and myogenin in later stage embryos[5]. As we have learned in this course, Pax3, MyoD, and myogenic are muscle cell differentiation factors.

To do this, IGF-2 promotes mTOR and MAPK pathways [5]. These pathways allow for protein synthesis.

3. Maternally Imprinted

Via researchgate.net

Although when one hears maternally imprinted they normally would think, "This gene will be expressed if mom shows it". However, that is not fully true for IGF-2. IGF-2 and H19 are controlled inversely of one another. So if mom is imprinting the enhancer to be on, she is actually enhancing H19 and silencing IGF-2; vice versa would also occur. Therefore, IGF-2 is paternally expressed because by mom imprinting it, she actually silences it and dad's version is expressed. [1]

4. Receptors Used

Via cell.com

IGF-2 uses the IGF-1 receptor [5]. Data has shown that on the IGF-1 Receptor, there may be different binding sites for IGF-1 and IGF-2 [4]. Furthermore, they have different affinities [2]. The affinities vary depending on the experimental conditions and type of cell [4].

IGF-2 uses the IGF-2 receptor for degradation of excessive IGF2- functioning like a scavenger receptor [4]. Without the IGF-2 receptor there would be overgrowth. Additionally, unlike the IGF gene itself, the receptor is expressed solely by the mother. [3]

5. Just for the prenatal?

Via news.stanford.edu

Although, IGF-2 was originally thought to only act prenatally, studies have shown that IGF-2 may also play a part in postnatal growth. Although not confirmed, the research suggested that IGF-2 possibly had greater expression postnatally. More research has to be done in this area to clarify these findings. This would help determine if hyperplasia or hypertrophy plays a larger role in the increased muscle gain [1].

Sources

[1] Clark, D. L., Clark, D. I., Beever, J. E., & Dilger, A. C. (2015). Increased prenatal IGF2 expression due to the porcine IGF2 intron3-G3072A mutation may be responsible for increased muscle mass. American Society of Animal Science.

[2] Clark, D. L., Clark, D. I., Hogen, E. K., Kroscher, K. A., & Dilger, A. C. (2015). Elevated insulin-like growth factor 2 expression may contribute to the hypermuscular phenotype of myostatin null mice. Growth Hormone & IGF Research.

[3] Kaku K, K., Osada H,, H., Seki, K., & Sekiya, S. (2007). Insulin-like growth factor 2 (IGF2) and IGF2 receptor gene variants are associated with fetal growth. Acta Paediatr.

[4] Li, R., Pourpak, A., & Morris*, S. W. (2010). Inhibition of the Insulin-like Growth Factor-1 Receptor (IGF1R) Tyrosine Kinase as a Novel Cancer Therapy Approach. Journal of Medicinal Chemistry.

[5] Mohammed, R. H., Anderton, H., Brameld, J. M., & Sweetman, D. (2017). Effects of insulin like growth factors on early embryonic chick limb myogenesis. PLOS One.