MGF (IGF-1Ec) 2000mcg

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Product Code: MG02
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Description

MGF (mechano growth factor), sometimes called IGF-1Ec, or the third isoform of IGF, is a growth factor peptide. MGF binds to IGF receptors and induces proliferation, in contrast to IGF-1. Some actions of MGF are mediated by different receptors or may be non-receptor-mediated. Physiologically, MGF is thought to hold a key role in localized tissue adaptation (muscular development and recovery) in physical exercise and pubertal development.

MGF is a locally expressed splice variant of full IGF-1 with a different E-domain. Endogenous MGF occurs in the context of a growth factor cascade involving other growth factors, as opposed to exogenous MGF administration. In the physiological context whereas IGF-1Ea (“normal” IGF) mainly circulates systemically, the other two isoforms (IGF1-Eb and IGF-1Ec/MGF) are expressed locally in an autocrine/paracrine fashion.

Yang and Goldspink (2006) write that “Unlike mature IGF-I, the distinct E domain of MGF inhibits terminal differentiation whilst increasing myoblast proliferation”[1]. MGF also induces proliferation (increase in number of cells)  in other tissue types under some circumstances[2]. This is opposite to the effect of normal IGF-1, which increases differentiation (maturation or specialization of young cells)[3].

Ates et al (2007) outline the differences and significance of IGF-1 vs MGF:

The effects of muscle splice variants of insulin-like growth factor I (IGF-I) on proliferation and differentiation were studied in human primary muscle cell cultures from healthy subjects as well as from muscular dystrophy and ALS patients. Although the initial numbers of mononucleated progenitor cells expressing desmin were lower in diseased muscle, the E domain peptide of IGF-IEc (MGF) significantly increased the numbers of progenitor cells in healthy and diseased muscle. IGF-I significantly enhances myogenic differentiation whereas MGF E peptide blocks this pathway, resulting in an increased progenitor (stem) cell pool and thus potentially facilitating repair and maintenance of this postmitotic tissue.[4]

Physiological MGF expression is context-dependent and is thought to be regulated by external factors such as exercise or damage:

The identification of a locally expressed, loading- or damage-sensitive IGF-1 isoform in skeletal muscle was one of the most attractive developments in the context of the autocrine/paracrine actions of IGF-1. ...competing processes of cellular proliferation and differentiation and the increased protein synthesis required for muscle repair or hypertrophic adaptation are regulated by a differential expression and by distinct roles of IGF-1 isoforms.[3]

The competing processes referred to by Philippou et al (2007) appear to be antagonistically controlled by opposition of circulating IGF-1 (inhibits proliferation, induces differentiation) and MGF (inhibits differentiation, induces proliferation)[3].

Another key difference between IGF-1 and MGF is that while IGF-1 has systemic actions and behaves according to the trajectory of lifespan and development, MGF acts primarily locally and in response to changes in environment and physiology:

insulin-like growth factor I (IGF-I) is an important growth factor for embryonic development, postnatal growth, tissue repair and maintenance of homeostasis. IGF-I functions and regulations are complex and tissue-specific. IGF-I mediates growth hormone signaling to target tissues during growth, but many IGF-I variants have been discovered, resulting in complex models to describe IGF-I function and regulation. Mechano-growth factor (MGF) is an alternative splicing variant of IGF-I and serves as a local tissue repair factor that responds to changes in physiological conditions or environmental stimuli. MGF expression is significantly increased in muscle, bone and tendon following damage resulting from mechanical stimuli and in the brain and heart following ischemia. MGF has been shown to activate satellite cells in muscle resulting in hypertrophy or regeneration, and functions as a neuroprotectant in brain ischemia. Both expression and processing of this IGF-I variant are tissue specific[5]

Research on human subjects involved in weight-training also supports the notion of MGF being involved in hypertrophy and post-exercise recovery. According to Wilborn et al (2009) 60-85% of 1-rep-max stimulates maximal expression of MHCs (myosin heavy chain isoforms) and growth factors including IGF-1Ec[6].

Citations
[1]Yang SY, Goldspink G. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett. 2002 Jul 3;522(1-3):156-60.
[2]Dai Z, Wu F, Yeung EW, Li Y. IGF-IEc expression, regulation and biological function in different tissues. Growth Horm IGF Res. 2010 May 20.
[3]Philippou A, Maridaki M, Halapas A, Koutsilieris M. The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology. In Vivo. 2007 Jan-Feb;21(1):45-54.
[4]Ates K, Yang SY, Orrell RW, Sinanan AC, Simons P, Solomon A, Beech S, Goldspink G, Lewis MP. The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle. FEBS Lett. 2007 Jun 12;581(14):2727-32.
[5]Dai Z, Wu F, Yeung EW, Li Y. IGF-IEc expression, regulation and biological function in different tissues. Growth Horm IGF Res. 2010 May 20.
[6]Wilborn CD, Taylor LW, Greenwood M, Kreider RB, Willoughby DS. Effects of different intensities of resistance exercise on regulators of myogenesis. J Strength Cond Res. 2009 Nov;23(8):2179-87.

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