Outstanding pubmed article showing how igf and mgf could be a great stack or is it?

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    Outstanding pubmed article showing how igf and mgf could be a great stack or is it?


    Growth factors and muscle ageing.

    Goldspink G, Harridge SD.

    Aximygen/UCL Biomedica, Division of Surgery, Royal Free and University College Medical School, The Archway Campus, 2-10 Highgate Hill, London N19 5LW, UK. goldspink@rfc.ucl.ac.uk

    Loss of muscle mass (sarcopenia) is one of the main problems associated with ageing as it has major health care as well as socioeconomic implications. The growth hormone (GH)/IGF-I axis is regarded as an important regulator of muscle mass. However, it is now appreciated that other tissues in addition to the liver express IGF-I and that there are local as well as systemic forms of IGF-I which have different functions. At least two different kinds of IGF-I that are expressed by skeletal muscle are derived from the IGF-I gene by alternative splicing, one of which is expressed in response to physical activity which has now been called 'mechano growth factor' (MGF). The other is similar to the systemic or liver type (IGF-IEa) and is important as the provider of mature IGF-I required for upregulating protein synthesis. MGF differs from systemic IGF-IEa in that it has a different peptide sequence which is responsible for replenishing the satellite (stem) cells in skeletal muscle. The ability to produce MGF declines with age, and this is commensurate with the decline in circulating GH levels. GH treatment up regulates the level of IGF-I gene expression in older people and when combined with resistance exercise more is spliced towards MGF and hence should improve the ability of muscle to respond to physical activity. The possibility of ameliorating sarcopenia using MGF is discussed.

    This is an outstanding article. I had been contemplating the effects of an IGF and MGF combined cycle because of some theories that I had been creating and I finally found evidence to back it! This article shows that increased IGF-1 actually creates more MGF through splicing, so its interesting to see whether or not it is even worth taking MGF when you can take IGF-1 and get the effects of both. However, we don't know how much is spliced towards it OR if the long chain r3 version can even be spliced towards MGF.

    If the latter is the case than it is interesting to see how an IGF + MGF cycle would be since the MGF replenishes the satellite cells that IGF uses to create hyperplasia!!!! MGF alone would almost be pointless because of this fact. We want hyperplasia NOT hypertrophy with this stuff guys.

    maybe I am on to something.

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    Great artical!!
    I was always under the impression that MGF and IGF-1 would be a great combo (as I beleive there is at least one member running both at the same time) but affording both at the same time is a luxery.
    As far as I know MGF has not been "advertised" (for the lack of a better word) for promoting hyperplasia (which there are studies I have read that mentioned hypersplasia along with hypertrophy, but this could could just have been "word pairing" ).

    Anywyas: NIce post!!
    I think we need a sticky somewhere (maybe included with the IGF sticky) on MGF,.. and any splice vairents we comne along in the future.
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    Re: Outstanding pubmed article showing how igf and mgf could be a great stack or is i


    Quote Originally Posted by xtraflossy
    Great artical!!
    I was always under the impression that MGF and IGF-1 would be a great combo (as I beleive there is at least one member running both at the same time) but affording both at the same time is a luxery.
    As far as I know MGF has not been "advertised" (for the lack of a better word) for promoting hyperplasia (which there are studies I have read that mentioned hypersplasia along with hypertrophy, but this could could just have been "word pairing" ).

    Anywyas: NIce post!!
    I think we need a sticky somewhere (maybe included with the IGF sticky) on MGF,.. and any splice vairents we comne along in the future.
    Yeah I actually created that MGF and IGF articles thread to be stickied, hopefully a mod will see this and do it for me. I add to my collection of IGF/MGF articles every day and I wouldn't mind doing so in the sticky thread too.

    Yea I had theorized for some time about IGF and MGF being great because of this pathway and it seemed to prove correct and I just happen to roll past this article.

    Heck maybe you and I should go in on IGF/MGF research as business partners since we seem to spend all of our time theorizing about it hahaha.
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    Re: Outstanding pubmed article showing how igf and mgf could be a great stack or is i


    Smoking gun number 2! Xtraflossy here is how you should set up your dosages or well when to do them anyways. MGF PWO and IGF later in the day, so a morning workout would work best if you could. However, after reading these results natural MGF levels were elevated for 5 days post workout with a peak at 4 days. I think it would be a great idea to do MGF injections in the to affected muscle about 5 days after the muscle is worked, you are still hitting a certain muscle every day but it was the muscle you worked 5 days ago. The igf needs to be consistently elevated so I recommend two injections of IGF per day split about 12 hours apart. Even if you are only doing 30-40mcg per day split them up and keep those numbers elevated. IGF lr3 doesn't have a 24 hour half life so it is best to split em.



    Muscle satellite (stem) cell activation during local tissue injury and repair
    Maria Hill,1 A. Wernig2 and G. Goldspink1
    Abstract

    In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin-like growth factor-I (IGF-I) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair.

    Time course of MGF and IGF-IEa expression

    The mRNA levels of the two types of IGF-I at different time intervals are shown in Fig. 3(a,b). From Fig. 3(a) it can be seen that MGF expression had peaked by the first measurement at 1 day in the case of mechanical damage and 4 days following bupivacaine injection. By contrast, the expression of IGF-IEa (Fig. 3b) was much slower and took 12 days to peak following bupivacaine injection. In the case of mechanical damage, IGF-IEa was still rising at 7 days whereas MGF mRNA levels had already declined to their original (non-damaged) control levels by this time.

    "The role of the growth-promoting properties of the E peptide in MGF, acting as an independent growth factor, is supported by the recent cell culture experiments of Yang & Goldspink (2002), in which stable transfection with MGF was shown to stimulate myoblast proliferation but differentiation was suppressed. The addition of a synthetic MGF peptide or the medium from MGF-transfected cells onto normal C2C12 cells also inhibited their differentiation. Yet this inhibition was reversed when the peptide or the medium were withdrawn. By contrast, cells of the liver type of systemic IGF-I (IGF-IEa)-positive clone did form myotubes and the normal cell lines showed less cellular proliferation as well as forming myotubes. Of particular interest was the observation that when an IGF-I receptor antibody was added to the muscle cell cultures, cell proliferation induced by MGF was not inhibited whereas their stimulation to increase in mass and to form myotubes by IGF-I was repressed. This result strongly suggests that MGF is involved in another signalling pathway in addition to that associated with the IGF-I receptor."


    "As MGF expression precedes M-cad mRNA and protein expression, this strongly suggests that this splice variant rather than IGF-IEa is involved in satellite cell activation. The latter (IGF-IEa) is expressed and peaks at 10 days following the insult. Although IGF-IEa is probably not involved in the initial activation of satellite cells, it is important that the repair process continues after the initial events and IGF-IEa is expressed at higher levels than MGF and is therefore a greater source of the mature peptide (IGF-I ligand domain). IGF-IEa expression may therefore be regarded as the second phase of local tissue repair as it is necessary to maintain protein synthesis rates in order to restore muscle mass."
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    Re: Outstanding pubmed article showing how igf and mgf could be a great stack or is i


    Quote Originally Posted by LakeMountD
    Smoking gun number 2! Xtraflossy here is how you should set up your dosages or well when to do them anyways. MGF PWO and IGF later in the day, so a morning workout would work best if you could.."
    Well, I had thought of that, but I dont have anything really do do another MGF cycle as I just spent the funds on some IGF-1 (and some x-factor / R-ALA / Blue-up stem free), Excel will be bought later along with Ectysterone at 3 grams daily= I dont want to Fu*K with my hormones for a long time, I didnt realize how freakn androgenic my natty test levels are that I have had back acne since I was 16; Damn, it feels good to feel good....... STACK)

    But I do agree; If I had some MGF I would divide my dosing:2 hours pre W/O and then post W/O. Despite others opinions, I have found this to be the most effective. Given post workout is a no-brainer that is. This is great because in the mornings, you then get another dose-among other things.
    ITs definately a NO-GO on morning workouts. I dont beleive the time of day matters,.. I'd rather make the changes with dosing and be able to have a more productive W/O. (plus,.. there are no hotties in the AM at Golds )



    Quote Originally Posted by LakeMountD
    The mRNA levels of the two types of IGF-I at different time intervals are shown in Fig. 3(a,b). From Fig. 3(a) it can be seen that MGF expression had peaked by the first measurement at 1 day in the case of mechanical damage and 4 days following bupivacaine injection. By contrast, the expression of IGF-IEa (Fig. 3b) was much slower and took 12 days to peak following bupivacaine injection. In the case of mechanical damage, IGF-IEa was still rising at 7 days whereas MGF mRNA levels had already declined to their original (non-damaged) control levels by this time.."
    I think I posted that exact same chart; This would have been before I received my MGF. I was looking for information on how much MGF the body expressed naturally in response to training./ I was able to get the level increases above Base, but couldnt find the sdtarting values. (would have made dosing MUCH easier).


    Quote Originally Posted by LakeMountD
    This result strongly suggests that MGF is involved in another signalling pathway in addition to that associated with the IGF-I receptor."
    HAHAHA -- already looking into it
    (expressing anything is never enopugh. Chemical reactions ALWAYS take place. In the case of local muscle damage, there must be a signal (MGF), that signal must then/in some way recruit "whateverX" by some means; and Im thinking there actually has to be a protein or something that has a certin coding to it, that may circulate until it runs into "WhateverX", ..which would take that coding (like an IP address) to tell it where to go. --= All speculation of some sort,.. but everything is chemical and such. The presence of MGF must signal IGF-1. We know that IGF signaling to that specific muscle group occurs at a later time (after MGF expression),.. which would indicate that simply "being there" doesnt elicit IGF-1 to speed up protein synthesis. It must be the release of a chemical messenger of sorts possibly from the breakup of MGF itself. (Please: dont tell me Im full of ****!! These are just guesses. Im tring to make sence of the magic with the knowlage that everything is action/reaction. If Im full of crap, .. Im sure I'll find out,...)


    Im always up for a business oppertunity. Theorizing about these things I would think is the easy part. Opinions are like *******s......Finding the studies on unrelated things to support the steps yopur taking to prove em' and connecting the factual dots is the hard part.

    ABOUT THE STICKY: Ya wanna put our heads together and come up with something??
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    Re: Outstanding pubmed article showing how igf and mgf could be a great stack or is i


    Quote Originally Posted by xtraflossy

    But I do agree; If I had some MGF I would divide my dosing:2 hours pre W/O and then post W/O. Despite others opinions, I have found this to be the most effective. Given post workout is a no-brainer that is. This is great because in the mornings, you then get another dose-among other things.
    I still don't think mgf should be injected into the worked muscle right aftery your workout. Look at that chart. Levels peaked in muscle on day 4. Why not do the injection on day 5 and keep them elevated in that area. I think mgf is best used as a way to help maybe two lagging muscle in your body since it is unreasonable to do it systemically or to try and hit every muscle because the results wouldn't be as pronounced as if you just did it in two muscle groups or so. Injecting on day 5, 6, and 7 into the lagging muscle group that you worked that long ag would see most logical then when y ou are ready to start working that muscle group on day 8 (or well it is day 1) then you can do your next three days of injections into the other lagging muscle group that was worked roughly 4-5 days ago. IGF needs to be taken throughout and like i said split up into two dosages. I MIGHT try a cycle of mgf + igf but man mgf is so expensive when looking at the dosages you have to take!
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    Well, First off, MOst people dont seem to like the idea of pinnin 12 hours boefore workout (all except the one other guy who tried it and loved it- ). That would be the same thing as pinning on day 8, one day before your next workout.
    In addition, It would appear that the peak level in that chart for MGF is about 1 day- if that. Also it appears to decline as IGF rises. I think that MGF expression is the preamble for repair in that it provides the "repair building blocks" (aka- when it causes neclui donation), and its IGF that does the actual repair (or the most part).
    Your body feels this is the best time (following injury) to express MGF in that tissue,.. And then there is some reaction that lowers that expression,..

    With MGF creating the neculi for repair and the hypertropic respons for adaptation, and based on my personal trials with MGF it would appear that tissue damage is a prerequisite for muscle GROWTH (saying nothing to maintaining muscle mass). Pinning MGF that many days after the majority of damage has been repaired seems to be wastefull.

    In addition,.. whatever lowers yoiur natural MGF expression in that tissue would more then likely "eat away" at the exogenous MGF your putting into it. -Nevermind the possible overexpression (after use) of what ever that particular factor may be; as it is already being expressed from from the end of day 1 (because of the lowering trend).

    "As MGF expression precedes M-cad mRNA and protein expression, this strongly suggests that this splice variant rather than IGF-IEa is involved in satellite cell activation. The latter (IGF-IEa) is expressed and peaks at 10 days following the insult. Although IGF-IEa is probably not involved in the initial activation of satellite cells, it is important that the repair process continues after the initial events and IGF-IEa is expressed at higher levels than MGF and is therefore a greater source of the mature peptide (IGF-I ligand domain). IGF-IEa expression may therefore be regarded as the second phase of local tissue repair as it is necessary to maintain protein synthesis rates in order to restore muscle mass."
    The quote doesnt say how long MGF is expressed, but the chart looks like its highest at about end of day1.
    Underlined part: Idealilly, MGF levels may hinder (or not be as effective) as MGF,.. so administration that far out may hinder gains my means not yet known

    -Of course I could be missinterpreting the chart-


    Here is the one I was refering to in regaurds to expressions after excersis- in relation to single vs. double bout excercise
    http://jap.physiology.org/content/vo...621583004.jpeg
    Last edited by xtraflossy; 03-21-2006 at 11:15 AM.
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    You are looking at MGF s/s, look at MGF bup, because that seems to be the one they refer to most when talking about muscle repair, that peaks at day 4. Not sure the differences between them yet since I haven't had a lot of time to really go in to it.

    I guess pwo mgf would be best assuming the levels that we are injecting are WELL over those that are present naturally in our muscles, which is kind of hard to tell since I don't believe there is a place that tests mgf levels in a blood pwo lol. I do think IGF is the missing link though with this IGF and I dont see mgf being all that great by itself due to this major fact. The upregulation of satellite cells is kind of a moot point unless you have something to actually form the repairs such as IGF-1 and the small amounts of circulating IGF naturally wouldn't seem to help much. THe nice thing about this MGF is that I believe you can SIGNFICANTLY INCREASE VOLUME of the lagging muscle and still recover from it with proper mgf and igf combined dosages due to the added mgf induced satellite cells as well as the increased repair rate of circulating IGF. Could make for some interesting results in the future. I might have to give it a try, only after I figure out how much MGF is enough though.
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    "The upregulation of satellite cells is kind of a moot point unless you have something to actually form the repairs such as IGF-1 and the small amounts of circulating IGF naturally wouldn't seem to help much. "


    Well, they obviously have been able to test MGF expression post work out. There just not listing the baseline,.. only the increases.

    I think your not giving the natural parts of your body enough credit. The current levels of IGF and hormones have been sufficiant for many years in repair. MGF post workout may actually increase levels of natural IGF-1, since there is a signaling process involved. The more MGF, the greater the need for IGF. We have been going through this cycle since the beginning, and never paying much attention to the two since we steped foot in the gym. It may be like the hormonal balance between testosterone and estrogen. Increase one and the body compensates for that overexpression.

    My case and point would be my most recent MGF administration. I trained legs yesterday. I killed them in squats. Then, I added some hard core sets for hamstrings. At this point I knew I'd never make it to work the next morning!!! After that even, I hopped on the legpress machine and did high rep (feet close together and high on the plate) to get me a piece of ass,.. which I also made sure to try and stress my hamstrings on the negatives.
    After the added sets: maxing the weight eventually on squats, so only 3 reps could be done,.. then hamstrings with the same technique (3 rep max reached after about 6 sets), then repitions on the leg press machine,.. I knew I was totally screwed.
    I only had 80mcg MGF remaining, so I pinned hamstrings.
    The result: Right now,.. Im having NO trouble walking!! Basicly there is NO soreness.
    Now, lately, I eat like Im bulking on leg day (dinner through bedtime). So, the callories were there. NO soreness!!!
    I might expect this added recovery in the hamstrings simply because I pinned the MGF post workout. (I dont know about volumn increases as I appears I forgot my tape measure at home). But, my glutes and quads are fine too!!! MGF aside, something more was at work aside from just the MGF- unless it ended up traveling into my quads and glutes when I injected my hamstrings. (40mcg each). Its a possibility.
    But given this increadable recovery where I would usually feel it 2 days later,.. I can only guess that the overexpression of MGF post workout caused some sort of increased expression in something else.
    I created the need (crazy leg damage)
    I gave a tool: (MGF: hamstrings) / diet
    My body was able to use both to its fullest advantage.
    -I guess thats the long way of saying I disagree with the statement where ya think that satalitte cell activation is a mute point W/O exogenous IGF.
    That being said- the inclusion of exo-IGF-1 should produce much greater results.
    But I beleive there is an Axis there between the 2. And the body tries to maintain the proper balances between the involved processes/hormones/reactions.
    If there wasn't an increase of anabolism of some sort I am at a loss to explain this expirence. The recovery time was just too damn fast.

    I'll see if I cant find anything on s/s Vs. bup (also, here is the articel I pulled my chart from: http://jap.physiology.org/cgi/content/full/93/1/394#F4 )

    -May be relative to determining normal MGF expression: Taken from artical- thought Id post it here so I would know where to find it later "However, when two exercise bouts were imposed, there appeared to be a trend toward an increase in total RNA (~10%) in the stimulated muscles at 24 and 40 h postexercise (data not shown). "


    Can anyone translate the bolded section????? - unit= ???
    ***However, the response of these mRNAs in the 24- and most notably the 48-h rest group was substantially greater than the increases seen with the other training paradigms. For example, an estimation of the MGF AUC for a single bout of exercise is 2.2 AUC units vs. 4.7 AUC units for the 48-h group. *** AUC= area under curve
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    "I think your not giving the natural parts of your body enough credit. The current levels of IGF and hormones have been sufficiant for many years in repair. MGF post workout may actually increase levels of natural IGF-1, since there is a signaling process involved."

    Acutally I don't think this is as much. Going from the article think about it. MGF is a spliced variation of IGF. I think your body produces the IGF after exercises, it gets spliced to mainly mgf but also the systemic version, your body continues to increase the amount of igf present in blood and splices more towards the systemic version and less towards mgf as time goes on.

    That is why I believe you need both to run the best possible cycle.

    I mean we don't know a lot of pathways but it seems MUCH more logical to me. The only other pathway I can think of is if your body sees too much mgf and begins to make more igf systemic variation to form repairs, but even in this case the dosages aren't near what we can inject pwo.

    I am giving the body credit but we all know it just cant keep up with what a needle can and when you are spending that much on mgf you might as well get the most out of it. We will see how everyones results go though, neither of us our doctors and through our friendly debate and article postings I am sure we will eventually come to a norm haha. Hell everyone from all over could be basing their cycles off of the stuff we post in this thread .
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    sounds easy enough to mix in same pin...would that work?
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    Re: Outstanding pubmed article showing how igf and mgf could be a great stack or is i


    Quote Originally Posted by anapolack
    sounds easy enough to mix in same pin...would that work?

    Read my article under the mgf results thread about the 3 day a week dosage scheme of igf and mgf.. seems th ebest way to do it is mgf on day 1 and 2 and igf on day 2 or 3-5.. read why in there..
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