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Peptide drawbacks?

i just got back from the car rental shop seeing as asshat and cock waffle fucked up my ride yesterday and i need something for my anniversary tomorrow. im still pissed had to vent srry. but anyways i saw a homeless chick who must of been on the glass dick or something walk up to me and say the sandwich was good.. but i would boned her. decent body for a hobo
 
CoBra666 said:
i just got back from the car rental shop seeing as asshat and cock waffle fucked up my ride yesterday and i need something for my anniversary tomorrow. im still pissed had to vent srry. but anyways i saw a homeless chick who must of been on the glass dick or something walk up to me and say the sandwich was good.. but i would boned her. decent body for a hobo
Click to expand...

Bahahaha...........I don't even know what to say.

So increased cortisol production makes you hungry as hell........that's not really a bad thing......

And I've heard that GHRP-6 at least will clean you out every morning......which is also not a bad thing......

So I'm still not hearing any actually bad side effects. And hurricane, I know that, anything will give you bad side effects if used incorrectly, but I'm wondering if you use peptides CORRECTLY if you'll have troubles with anything.
 
So I'm trying to dig up info on GHRPs, GHRHs, CJC, etc...

and I was wondering what the drawbacks or side effects are of various peptides?

I mean, I've had a hard time finding negative side effects on these things but I've yet to find a substance that doesn't have any drawbacks.

Any insight on that?

Honestly you need to do your own indepth research on each one untill you know the ins and outs.
I highly rec PP's ( Purchase Peptides ) IGF1LR3 myself.

here is some basic info though:
[FONT=&quot]INFO: GHRP-6 (Growth Hormone Releasing Peptide – 6)[/FONT]
[FONT=&quot]GHRP-6: GHRP-6 (Growth Hormone Releasing Peptide – 6) is a hexapeptide with a chain comprised of 6 amino acids. This special sequence is considered to provide a signal to the body to begin secreting Growth Hormone(GH) release while also blocking Somatostatin, a hormone that inhibits Growth Hormone release. Growth Hormone has host of beneficial effects such as decreased body fat, increased muscle, and increased strength and stamina so maximizing the production and secretion can be a great addition to improved animal physical shape. Increased amounts of Growth Hormone then can cause the Liver to secrete the hormone IGF-1 which has also been implicated in improving the animal body’s ability to burn fat and build muscle. Clinical cases have shown that the use of GHRP-6 was associated with increased muscle mass and a reduction of body fat.

Dosage - 250-500mcg daily [/FONT]


[FONT=&quot]Growth hormone releasing hexapeptide[/FONT]
[FONT=&quot]From Wikipedia, the free encyclopedia[/FONT]
[FONT=&quot]Growth hormone releasing hexapeptide[/FONT]​
[FONT=&quot]IUPAC name[/FONT][FONT=&quot][hide][/FONT]​
[FONT=&quot]L-histidyl-D-tryptophyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-Lysinamide[/FONT]​
[FONT=&quot]Other names[/FONT][FONT=&quot][hide][/FONT]​
[FONT=&quot]GHRP-6[/FONT]​
[FONT=&quot]Growth hormone releasing hexapeptide[/FONT][FONT=&quot] (GHRP6) is one of several synthetic [/FONT][FONT=&quot]met-enkephalin[/FONT][FONT=&quot] analogs that include unnatural D-amino acids, were developed for their [/FONT][FONT=&quot]growth hormone[/FONT][FONT=&quot] (GH) releasing activity and are called GH secretagogues. They lack [/FONT][FONT=&quot]opioid[/FONT][FONT=&quot] activity but are potent stimulators of GH release. These secretagogues are distinct from [/FONT][FONT=&quot]growth hormone releasing hormone[/FONT][FONT=&quot] (GHRH) in that they share no sequence relation and derive their function through action at a completely different receptor. This receptor was originally called the GH secretagogue receptor, the hormone [/FONT][FONT=&quot]ghrelin[/FONT][FONT=&quot] is now considered the receptor's natural endogenous ligand. Therefore, these GH secretagouges act as synthetic ghrelinmimetics.[/FONT]
[FONT=&quot]The major side effect accompanied by the use of GHRP-6 or other GH secretagogues is a significant increase in appetite because secretagogues mimic the action of Ghrelin, a peptide which is released naturally in the lining of the stomach and increases hunger and gastric emptying.[/FONT]
[FONT=&quot]GHRP-6, other secretagogues and ghrelin stimulate the anterior pituitary gland causing an increase in GH release. When natural GH secretion has been inhibited by long term abuse of synthetic GH, GHRP-6 may help to re-stimulate the natural production of GH. GHRP-6 may also affect the central nervous system by protecting neurons as well as increasing strength in a way very similar to the way certain steroids in the Dihydrotestosterone family do.[/FONT]
[FONT=&quot]Claimed benefits of increased Growth Hormone levels through GHRP-6 stimulation include: an increase in strength, muscle mass and body fat loss, rejuvenation and strengthening of joints, connective tissue and bone mass. Enhanced GH secretion also leads to the liver secreting more IGF-1 (Insulin-Like Growth Factor 1), which is thought to be the primary anabolic mechanism of action for Growth Hormone.[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Technical data[/FONT]
[FONT=&quot]It has also been discovered that when GHRP-6 and insulin are used simultaneously, GH response to GHRP-6 is increased (1). A recent study in normal mice showed significant differences in body composition, muscle growth, glucose metabolism, memory and cardiac function in the mice being administered the GHRP-6 (2). There are still many questions regarding this fairly new compound, scientists are hoping to gain a better clinical understanding of the peptide through further research over the next few years.[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] References[/FONT]


  • [FONT=&quot]{{Penlava, A, et. al. Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, [/FONT][FONT=&quot]pyridostigmine[/FONT][FONT=&quot], or hypoglycemia on GHRP-6-induced GH secretion in man.}}[/FONT]


-0-------------------------------------------------------
[FONT=&quot]Growth Hormone Releasing Peptide - 2 (GHRP2)[/FONT]
[FONT=&quot]Is a synthetic six amino acid peptide that has robustly potent properties.[/FONT]
[FONT=&quot]GHRPs are a small family of peptides acting at the pituitary and the hypothalamus to release Growth hormone (GH) through the activation of a specific, G protein-coupled receptor. [/FONT]
[FONT=&quot]They were discovered 20 years ago as synthetic metenkephalin- derived oligopeptides (Synthetic tissue derived amino acids). Although it has no structural homology with Growth Hormone Releasing Hormone (GHRH), in clinical studies GHRP-2 demonstrated action on the pituitary to release Human Growth Hormone (HGH). Similar results were effective when GHRP-2 was administered sublingual. Clinical studies showed the most potent GHRP being the hexapeptide GHRP-2.[/FONT]
[FONT=&quot]Growth Hormone Releasing Peptide 2(GHRP2) substantially stimulates the pituitary gland's increased natural production of the body's own endogenous human growth hormone (HGH). This therapy consists of daily periodic sub-lingual dosing. Growth Hormone releasing peptide 2, GHRP2 has shown on it's own to robustly increase IGF-1 levels, and even greater results occurred when used with Growth Hormone Releasing Hormone (GHRH) to which also stimulates the pituitary gland to produce increased natural secretion of human growth hormone. This also boosts the hypothalamus function as well.[/FONT]
[FONT=&quot]The results of the clinical studies published in the Journal of Endocrinology and Metabolism in 1997 for GHRP2 - showed that a medically supervised, prescribed and administered therapy increased growth hormone levels in adults and children, who have growth hormone deficiency.[/FONT]
[FONT=&quot]The increase in the body's growth hormone via elevated IGF-1 levels produced by the pituitary gland in response to GHRP2 therapy -- has an anabolic effect on the tissues of the body and other benefits identified below.[/FONT]
[FONT=&quot]Synergy of GHRH + GHRP[/FONT]

[FONT=&quot]It is well documented and established that the concurrent administration of Growth Hormone Releasing Hormone (GHRH) and a Growth Hormone Releasing Peptide (GHRP-6, GHRP-2 or Hexarelin) results in synergistic release of GH from pituitary stores. In other words if GHRH contributes a GH amount quantified as the number 2 and GHRPs contributed a GH amount quantified as the number 4 the total GH release is not additive (i.e. 2 + 4 = 6). Rather the whole is greater than the sum of the parts such that 2 + 4 = 10.[/FONT]

[FONT=&quot]While the GHRPs (GHRP-6, GHRP-2 and Hexarelin) come in only one half-life form and are capable of generating a GH pulse that lasts a couple of hours re-administration of a GHRP is required to effect additional pulses.[/FONT]

[FONT=&quot]Growth Hormone Releasing Hormone (GHRH) however is currently available in several forms which vary only by their half-lives. Naturally occurring GHRH is either a 40 or 44 amino acid peptide with the bioactive portion residing in the first 29 amino acids. This shortened peptide identical in behavior and half-life to that of GHRH is called Growth Hormone Releasing Factor and is abbreviated as GRF(1-29).[/FONT]

[FONT=&quot]GRF(1-29) is produced and sold as a drug called Sermorelin. It has a short-half life measured in minutes. If you prefer analogies think of this as a Testosterone Suspension (i.e. unestered).[/FONT]

[FONT=&quot]To increase the stability and half-life of GRF(1-29) four amino acid changes where made to its structure. These changes increase the half-life beyond 30 minutes which is more than sufficient to exert a sustained effect which will maximize a GH pulse. This form is often called tetrasubstituted GRF(1-29) (or modified) and unfortunately & confusingly mislabeled as CJC-1295. If you prefer analogies think of this as a Testosterone Propionate (i.e. short-estered).[/FONT]

[FONT=&quot]Note that some may also refer to this as CJC-1295 without the DAC (Drug Affinity Complex).[/FONT]

[FONT=&quot]Frequent dosing of either the aforementioned modified GRF(1-29) or regular GRF(1-29) is required and as previously indicated works synergistically with a GHRP.[/FONT]

[FONT=&quot]In an attempt to create a more convenient long-lasting GHRH, a compound known as CJC-1295 was created. This compound is identical to the aforementioned modified GRF(1-29) with the addition of the amino acid Lysine which links to a non-peptide molecule known as a "Drug Affinity Complex (DAC)". This complex allows GRF(1-29) to bind to albumin post-injection in plasma and extends its half-life to that of days. If you prefer analogies think of this as a Testosterone Cypionate (i.e. long-estered). However this is not accurate. CJC-1295 results in continual GH bleed. Although natural pulsation still occurs CJC-1295 does nothing to increase those pulses. Instead it raises base levels of GH and creates a more feminized pattern of release. This not desirable.[/FONT]

[FONT=&quot]Modified GRF(1-29)however when combined with a GHRP brings about a substantial pulse which has desirable effects.[/FONT]

[FONT=&quot]A Brief Summary of Dosing and Administration[/FONT]

[FONT=&quot]Dosing GHRPs[/FONT]

[FONT=&quot]The saturation dose in most studies on the GHRPs (GHRP-6, GHRP-2, Ipamorelin & Hexarelin) is defined as either 100mcg or 1mcg/kg.[/FONT]

[FONT=&quot]What that means is that 100mcg will saturate the receptors fully, but if you add another 100mcg to that dose only 50% of that portion will be effective. If you add an additional 100mcg to that dose only about 25% will be effective. Perhaps a final 100mcg might add a little something to GH release but that is it.[/FONT]

[FONT=&quot]So 100mcg is the saturation dose and you could add more up to 300 to 400mcg and get a little more effect.[/FONT]

[FONT=&quot]A 500mcg dose will not be more effective then a 400mcg, perhaps not even more effective then 300mcg.[/FONT]

[FONT=&quot]The additional problems are desensitization & cortisol/prolactin side-effects.[/FONT]
--------------------------------------
[FONT=&quot]Insulin-like growth factor 1[/FONT]
[FONT=&quot]Insulin-like growth factor 1[/FONT]
​
[FONT=&quot][2][/FONT]

[FONT=&quot]Insulin-like growth factor 1[/FONT][FONT=&quot] (IGF-1) also known as somatomedin C or mechano growth factor is a [/FONT][FONT=&quot]protein[/FONT][FONT=&quot] that in humans is encoded by the IGF1 [/FONT][FONT=&quot]gene[/FONT][FONT=&quot].[/FONT][FONT=&quot][1][/FONT][FONT=&quot][2][/FONT][FONT=&quot] IGF-1 has also been referred to as a "sulfation factor"[/FONT][FONT=&quot][3][/FONT][FONT=&quot] and its effects were termed "nonsuppressible insulin-like activity" (NSILA) in the 1970s.[/FONT]
[FONT=&quot]IGF-1 is a [/FONT][FONT=&quot]hormone[/FONT][FONT=&quot] similar in [/FONT][FONT=&quot]molecular structure[/FONT][FONT=&quot] to [/FONT][FONT=&quot]insulin[/FONT][FONT=&quot]. It plays an important role in childhood growth and continues to have [/FONT][FONT=&quot]anabolic effects[/FONT][FONT=&quot] in adults. A synthetic analog of IGF-1, [/FONT][FONT=&quot]mecasermin[/FONT][FONT=&quot] is used for the treatment of [/FONT][FONT=&quot]growth failure[/FONT][FONT=&quot].[/FONT][FONT=&quot][4][/FONT]
[FONT=&quot]IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges. IGF-1 has a molecular weight of 7649 daltons.[/FONT]
[FONT=&quot]Contents[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]hide[/FONT][FONT=&quot]][/FONT]

[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Synthesis and circulation[/FONT]
[FONT=&quot]IGF-1 is produced primarily by the [/FONT][FONT=&quot]liver[/FONT][FONT=&quot] as an [/FONT][FONT=&quot]endocrine[/FONT][FONT=&quot] hormone as well as in target tissues in a paracrine/autocrine fashion. Production is stimulated by [/FONT][FONT=&quot]growth hormone[/FONT][FONT=&quot] (GH) and can be retarded by undernutrition, growth hormone insensitivity, lack of growth hormone receptors, or failures of the downstream signalling pathway post GH receptor including [/FONT][FONT=&quot]SHP2[/FONT][FONT=&quot] and [/FONT][FONT=&quot]STAT5B[/FONT][FONT=&quot]. Approximately 98% of IGF-1 is always bound to one of 6 binding proteins (IGF-BP). [/FONT][FONT=&quot]IGFBP-3[/FONT][FONT=&quot], the most abundant protein, accounts for 80% of all IGF binding. IGF-1 binds to IGFBP-3 in a 1:1 molar ratio.[/FONT]
[FONT=&quot]In rat experiments the amount of IGF-1 mRNA in the liver was positively associated with dietary [/FONT][FONT=&quot]casein[/FONT][FONT=&quot] and negatively associated with a protein free diet.[/FONT][FONT=&quot][5][/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Mechanism of action[/FONT]
[FONT=&quot]Its primary action is mediated by binding to its specific receptor, the [/FONT][FONT=&quot]Insulin-like growth factor 1 receptor[/FONT][FONT=&quot], abbreviated as ""[/FONT][FONT=&quot]IGF1R[/FONT][FONT=&quot]"", present on many cell types in many tissues. Binding to the IGF1R, a [/FONT][FONT=&quot]receptor tyrosine kinase[/FONT][FONT=&quot], initiates intracellular signaling; IGF-1 is one of the most potent natural activators of the [/FONT][FONT=&quot]AKT[/FONT][FONT=&quot]signaling pathway[/FONT][FONT=&quot], a stimulator of cell growth and proliferation, and a potent inhibitor of [/FONT][FONT=&quot]programmed cell death[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]IGF-1 is a primary mediator of the effects of [/FONT][FONT=&quot]growth hormone[/FONT][FONT=&quot] (GH). [/FONT][FONT=&quot]Growth hormone[/FONT][FONT=&quot] is made in the [/FONT][FONT=&quot]anterior pituitary[/FONT][FONT=&quot] gland, is released into the blood stream, and then stimulates the [/FONT][FONT=&quot]liver[/FONT][FONT=&quot] to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every [/FONT][FONT=&quot]cell[/FONT][FONT=&quot] in the body, especially skeletal [/FONT][FONT=&quot]muscle[/FONT][FONT=&quot], [/FONT][FONT=&quot]cartilage[/FONT][FONT=&quot], [/FONT][FONT=&quot]bone[/FONT][FONT=&quot], [/FONT][FONT=&quot]liver[/FONT][FONT=&quot], [/FONT][FONT=&quot]kidney[/FONT][FONT=&quot], [/FONT][FONT=&quot]nerves[/FONT][FONT=&quot], [/FONT][FONT=&quot]skin[/FONT][FONT=&quot], [/FONT][FONT=&quot]hematopoietic[/FONT][FONT=&quot] cell, and [/FONT][FONT=&quot]lungs[/FONT][FONT=&quot]. In addition to the [/FONT][FONT=&quot]insulin[/FONT][FONT=&quot]-like effects, IGF-1 can also regulate [/FONT][FONT=&quot]cell growth[/FONT][FONT=&quot] and development, especially in nerve cells, as well as cellular [/FONT][FONT=&quot]DNA[/FONT][FONT=&quot] synthesis.[/FONT]
[FONT=&quot]Deficiency of either [/FONT][FONT=&quot]growth hormone[/FONT][FONT=&quot] or IGF-1 therefore results in diminished stature. GH-deficient children are given [/FONT][FONT=&quot]recombinant[/FONT][FONT=&quot] GH to increase their size. IGF-1 deficient humans, who are categorized as having [/FONT][FONT=&quot]Laron syndrome[/FONT][FONT=&quot], or Laron's dwarfism, are treated with recombinant IGF-1. In beef cattle, circulating IGF-I concentrations are related to reproductive performance.[/FONT][FONT=&quot][6][/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Receptors[/FONT]
[FONT=&quot]IGF-1 binds to at least two cell surface receptors: the [/FONT][FONT=&quot]IGF-1 receptor[/FONT][FONT=&quot] (IGF1R), and the [/FONT][FONT=&quot]insulin receptor[/FONT][FONT=&quot]. The [/FONT][FONT=&quot]IGF-1 receptor[/FONT][FONT=&quot] seems to be the "physiologic" receptor - it binds IGF-1 at significantly higher affinity than the IGF-1 that is bound to the insulin receptor. Like the insulin receptor, the IGF-1 receptor is a receptor [/FONT][FONT=&quot]tyrosine kinase[/FONT][FONT=&quot] - meaning it signals by causing the addition of a phosphate molecule on particular tyrosines. IGF-1 activates the insulin receptor at approximately 0.1x the potency of insulin. Part of this signaling may be via IGF1R/Insulin Receptor heterodimers (the reason for the confusion is that binding studies show that IGF1 binds the insulin receptor 100-fold less well than insulin, yet that does not correlate with the actual potency of IGF1 in vivo at inducing phosphorylation of the insulin receptor, and hypoglycemia)..[/FONT]
[FONT=&quot]IGF-1 is produced throughout life. The highest rates of IGF-1 production occur during the pubertal growth spurt. The lowest levels occur in infancy and old age.[/FONT]
[FONT=&quot]Other IGFBPs are inhibitory. For example, both [/FONT][FONT=&quot]IGFBP-2[/FONT][FONT=&quot] and [/FONT][FONT=&quot]IGFBP-5[/FONT][FONT=&quot] bind IGF-1 at a higher affinity than it binds its receptor. Therefore, increases in serum levels of these two IGFBPs result in a decrease in IGF-1 activity.[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Related growth factors[/FONT]
[FONT=&quot]IGF-1 is closely related to a second protein called "[/FONT][FONT=&quot]IGF-2[/FONT][FONT=&quot]". IGF-2 also binds the IGF-1 receptor. However, IGF-2 alone binds a receptor called the "IGF II receptor" (also called the mannose-6 phosphate receptor). The insulin growth factor-II receptor (IGF2R) lacks signal transduction capacity, and its main role is to act as a sink for IGF-2 and make less IGF-2 available for binding with IGF-1R. As the name "insulin-like growth factor 1" implies, IGF-1 is structurally related to insulin, and is even capable of binding the insulin receptor, albeit at lower affinity than insulin.[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Regulation of aging[/FONT]
[FONT=&quot]The [/FONT][FONT=&quot]daf-2[/FONT][FONT=&quot]gene[/FONT][FONT=&quot] encodes an [/FONT][FONT=&quot]insulin[/FONT][FONT=&quot]-like [/FONT][FONT=&quot]receptor[/FONT][FONT=&quot] in the worm [/FONT][FONT=&quot]C. elegans[/FONT][FONT=&quot]. [/FONT][FONT=&quot]Mutations[/FONT][FONT=&quot] in daf-2 have been shown by [/FONT][FONT=&quot]Cynthia Kenyon[/FONT][FONT=&quot] to double the lifespan of the worms.[/FONT][FONT=&quot][7][/FONT][FONT=&quot] The gene is known to regulate reproductive development, aging, resistance to [/FONT][FONT=&quot]oxidative stress[/FONT][FONT=&quot], thermotolerance, resistance to [/FONT][FONT=&quot]hypoxia[/FONT][FONT=&quot], and also resistance to bacterial [/FONT][FONT=&quot]pathogens[/FONT][FONT=&quot].[/FONT][FONT=&quot][8][/FONT]
[FONT=&quot]DAF-2 is the only insulin/[/FONT][FONT=&quot]IGF-1[/FONT][FONT=&quot] like receptor in the worm. Insulin/[/FONT][FONT=&quot]IGF-1[/FONT][FONT=&quot]-like signaling is conserved from worms to [/FONT][FONT=&quot]humans[/FONT][FONT=&quot]. DAF-2 acts to negatively regulate the forkhead [/FONT][FONT=&quot]transcription factor[/FONT][FONT=&quot] DAF-16 through a [/FONT][FONT=&quot]phosphorylation[/FONT][FONT=&quot] cascade. Genetic analysis reveals that DAF-16 is required for daf-2-dependent lifespan extension and dauer formation. When not phosphorylated, DAF-16 is active and present in the [/FONT][FONT=&quot]nucleus[/FONT][FONT=&quot].[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Factors influencing the levels in the circulation[/FONT]
[FONT=&quot][/FONT]
[FONT=&quot][/FONT]
[FONT=&quot]3-d model of IGF-1[/FONT]
[FONT=&quot]Factors that are known to cause variation in the levels of [/FONT][FONT=&quot]growth hormone[/FONT][FONT=&quot] (GH) and IGF-1 in the circulation include: genetic make-up, the time of day, age, sex, exercise status, stress levels, nutrition level and body mass index (BMI), disease state, race, estrogen status and [/FONT][FONT=&quot]xenobiotic[/FONT][FONT=&quot] intake.[/FONT][FONT=&quot][9][/FONT][FONT=&quot] The later inclusion of xenobiotic intake as a factor influencing GH-IGF status highlights the fact that the GH-IGF axis is a potential target for certain endocrine disrupting chemicals - see also [/FONT][FONT=&quot]endocrine disruptor[/FONT][FONT=&quot].[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Diseases of deficiency and resistance[/FONT]
[FONT=&quot]Rare diseases characterized by inability to make or respond to IGF-1 produce a distinctive type of growth failure. One such disorder, termed [/FONT][FONT=&quot]Laron dwarfism[/FONT][FONT=&quot] does not respond at all to [/FONT][FONT=&quot]growth hormone treatment[/FONT][FONT=&quot] due to a lack of GH receptors. The FDA has grouped these diseases into a disorder called severe primary IGF deficiency. Patients with severe primary IGFD typically present with normal to high GH levels, height below -3 standard deviations (SD), and IGF-1 levels below -3SD. Severe primary IGFD includes patients with mutations in the GH receptor, post-receptor mutations or IGF mutations, as previously described. As a result, these patients cannot be expected to respond to GH treatment.[/FONT]
[FONT=&quot]The IGF signaling pathway appears to play a crucial role in cancer. Several studies have shown that increased levels of IGF lead to an increased risk of cancer.[[/FONT][FONT=&quot]citation needed[/FONT][FONT=&quot]][/FONT][FONT=&quot] Studies done on lung cancer cells show that drugs inhibiting such signaling can be of potential interest in cancer therapy.[/FONT][FONT=&quot][10][/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Use as a diagnostic test[/FONT]

[FONT=&quot]IGF-1 levels can be measured in the blood in 10-1000 ng/ml amounts. As levels do not fluctuate greatly throughout the day for an individual person, IGF-1 is used by physicians as a [/FONT][FONT=&quot]screening test[/FONT][FONT=&quot] for [/FONT][FONT=&quot]growth hormone deficiency[/FONT][FONT=&quot] and [/FONT][FONT=&quot]excess[/FONT][FONT=&quot] in [/FONT][FONT=&quot]acromegaly[/FONT][FONT=&quot] and [/FONT][FONT=&quot]gigantism[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]Interpretation of IGF-1 levels is complicated by the wide normal ranges, and variations by age, sex, and pubertal stage. Clinically significant conditions and changes may be masked by the wide normal ranges. Sequential management over time is often useful for the management of several types of pituitary disease, undernutrition, and growth problems.[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] As a therapeutic agent[/FONT]
[FONT=&quot]Mecasermin[/FONT][FONT=&quot] (brand name Increlex) is a synthetic analog of IGF-1 which is approved for the treatment of [/FONT][FONT=&quot]growth failure[/FONT][FONT=&quot].[/FONT][FONT=&quot][12][/FONT][FONT=&quot] IGF-1 has been manufactured recombinantly on a large scale using both yeast and E. coli.[/FONT]
[FONT=&quot]Several companies have evaluated IGF-1 in clinical trials for a variety of additional indications, including [/FONT][FONT=&quot]type 1 diabetes[/FONT][FONT=&quot], [/FONT][FONT=&quot]type 2 diabetes[/FONT][FONT=&quot], [/FONT][FONT=&quot]amyotrophic lateral sclerosis[/FONT][FONT=&quot] (ALS aka "Lou Gehrig's Disease"), severe burn injury and myotonic muscular dystrophy (MMD). Results of clinical trials evaluating the efficacy of IGF-1 in type 1 diabetes and type 2 diabetes showed great promise in reducing hemoglobin A1C levels, as well as daily insulin consumption. However, the sponsor, [/FONT][FONT=&quot]Genentech[/FONT][FONT=&quot], discontinued the program due to an exacerbation of diabetic retinopathy[citation needed] in patients coupled with a shift in corporate focus towards oncology. Cephalon and Chiron conducted two pivotal clinical studies of IGF-1 for ALS, and although one study demonstrated efficacy, the second was equivocal, and the product has never been approved by the FDA.[/FONT]
[FONT=&quot]However, in the last few years, two additional companies [/FONT][FONT=&quot]Tercica[/FONT][FONT=&quot] and [/FONT][FONT=&quot]Insmed[/FONT][FONT=&quot] compiled enough clinical trial data to seek FDA approval in the United States. In August 2005, the FDA approved Tercica's IGF-1 drug, Increlex, as replacement therapy for severe primary IGF-1 deficiency based on clinical trial data from 71 patients. In December 2005, the FDA also approved Iplex, Insmed's IGF-1/IGFBP-3 complex. The Insmed drug is injected once a day versus the twice-a-day version that Tercica sells.[/FONT]
[FONT=&quot]Insmed was found to infringe on patents licensed by Tercica, which then sought to get a U.S. district court judge to ban sales of Iplex.[/FONT][FONT=&quot][13][/FONT][FONT=&quot] To settle patent infringement charges and resolve all litigation between the two companies, Insmed in March 2007 agreed to withdraw Iplex from the U.S. market, leaving Tercica's Increlex as the sole version of IGF-1 available in the United States.[/FONT][FONT=&quot][14][/FONT]
[FONT=&quot]By delivering Iplex in a complex, patients might get the same efficacy with regard to growth rates but experience fewer side effects with less severe hypoglycemia[citation needed]. This medication might emulate IGF-1's endogenous complexing, as in the human body 97-99% of IGF-1 is bound to one of six [/FONT][FONT=&quot]IGF binding proteins[/FONT][FONT=&quot][[/FONT][FONT=&quot]citation needed[/FONT][FONT=&quot]][/FONT][FONT=&quot]. IGFBP-3 is the most abundant of these binding proteins, accounting for approximately 80% of IGF-1 binding.[/FONT]
[FONT=&quot]In a clinical trial of an investigational compound MK-677, which raises IGF-1 in patients, did not result in an improvement in patients' Alzheimer's symptoms.[/FONT][FONT=&quot][15][/FONT][FONT=&quot] Another clinical demonstrated that Cephalon's IGF-1 does not slow the progression of weakness in ALS patients. Previous shorter studies had conflicting results.[/FONT][FONT=&quot][16][/FONT]
[FONT=&quot]IGFBP-3[/FONT][FONT=&quot] is a carrier for IGF-1, meaning that IGF-1 binds [/FONT][FONT=&quot]IGFBP-3[/FONT][FONT=&quot], creating a complex whose combined molecular weight and binding affinity allows the growth factor to have an increased half-life in serum. Without binding to [/FONT][FONT=&quot]IGFBP-3[/FONT][FONT=&quot], IGF-1 is cleared rapidly through the kidney, due to its low molecular weight. But when bound to [/FONT][FONT=&quot]IGFBP-3[/FONT][FONT=&quot], IGF-1 evades renal clearance. Also, since IGFBP-3 has a lower affinity for IGF-1 than IGF-1 has for its receptor, [/FONT][FONT=&quot]IGFR[/FONT][FONT=&quot], its binding does not interfere with IGF-1 function. For these reasons, an IGF-1/[/FONT][FONT=&quot]IGFBP-3[/FONT][FONT=&quot] combination approach was approved for human treatment... brought forward by a small company called Insmed. However, Insmed fell afoul patent issues, and was ordered to desist in this approach.[/FONT]
[FONT=&quot]IGF-1 has also been shown to be effective in animal models of stroke when combined with Erythropoietin. Both behavioural and cellular improvements were found.[/FONT][FONT=&quot][17][/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Interactions[/FONT]
[FONT=&quot]Insulin-like growth factor 1 has been shown to bind and interact with all the IGF-1 Binding Proteins (IGFBPs), of which there are six (IGFBP1-6).[/FONT]
[FONT=&quot]Specific references are provided for [/FONT][FONT=&quot]interactions[/FONT][FONT=&quot] with [/FONT][FONT=&quot]IGFBP3[/FONT][FONT=&quot],[/FONT][FONT=&quot][18][/FONT][FONT=&quot][19][/FONT][FONT=&quot][20][/FONT][FONT=&quot][21][/FONT][FONT=&quot][22][/FONT][FONT=&quot][23][/FONT][FONT=&quot]IGFBP4[/FONT][FONT=&quot],[/FONT][FONT=&quot][24][/FONT][FONT=&quot][25][/FONT][FONT=&quot] and [/FONT][FONT=&quot]IGFBP7[/FONT][FONT=&quot].[/FONT][FONT=&quot][26][/FONT][FONT=&quot][27][/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] References[/FONT]
[FONT=&quot]1. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Höppener JW, de Pagter-Holthuizen P, Geurts van Kessel AH, Jansen M, Kittur SD, Antonarakis SE, Lips CJ, Sussenbach JS (1985). "The human gene encoding insulin-like growth factor I is located on chromosome 12". Hum. Genet. 69 (2): 157–60. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1007/BF00293288[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]2982726[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]2. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Jansen M, van Schaik FM, Ricker AT, Bullock B, Woods DE, Gabbay KH, Nussbaum AL, Sussenbach JS, Van den Brande JL (1983). "Sequence of cDNA encoding human insulin-like growth factor I precursor". Nature 306 (5943): 609–11. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1038/306609a0[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]6358902[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]3. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Salmon W, Daughaday W (1957). "A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro". J Lab Clin Med 49 (6): 825–36. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]13429201[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]4. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Keating GM (2008). "Mecasermin". BioDrugs 22 (3): 177–88. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.2165/00063030-200822030-00004[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]18481900[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]5. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Miura, Y.; Kato, H.; Noguchi, T. (2007). "Effect of dietary proteins on insulin-like growth factor-1 (IGF-1) messenger ribonucleic acid content in rat liver". British Journal of Nutrition 67 (2): 257. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1079/BJN19920029[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]1596498[/FONT][FONT=&quot]. [/FONT][FONT=&quot]edit[/FONT]
[FONT=&quot]6. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Yilmaz A, Davis ME, RCM Simmen RCM (1999). "Reproductive performance of bulls divergently selected on the basis of blood serum insulin-like growth factor I concentration". J Anim Sci 77 (4): 835–9.[/FONT]
[FONT=&quot]7. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] See publications documenting series of experiments at [/FONT][FONT=&quot]Cynthia Kenyon lab[/FONT][FONT=&quot], in particular, Dorman JB, Albinder B, Shroyer T, Kenyon C (December 1995). [/FONT][FONT=&quot]"The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans"[/FONT][FONT=&quot]. Genetics 141 (4): 1399–406. [/FONT][FONT=&quot]PMC[/FONT][FONT=&quot]1206875[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]8601482[/FONT][FONT=&quot].; and Apfeld J, Kenyon C (October 1998). "Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span". Cell 95 (2): 199–210. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1016/S0092-8674(00)81751-1[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]9790527[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]8. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Minaxi S Gami and Catherine A Wolkow (2006). [/FONT][FONT=&quot]"Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for pharmacological manipulation of lifespan"[/FONT][FONT=&quot]. Aging Cell 5 (1): 31. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1111/j.1474-9726.2006.00188.x[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMC[/FONT][FONT=&quot]1413578[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]16441841[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]9. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Scarth J (2006). "Modulation of the growth hormone-insulin-like growth factor (GH-IGF) axis by pharmaceutical, nutraceutical and environmental xenobiotics: an emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review". Xenobiotica 36 (2-3): 119–218. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1080/00498250600621627[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]16702112[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]10. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Velcheti V, Govindan R (2006). [/FONT][FONT=&quot]"Insulin-like growth factor and lung cancer"[/FONT][FONT=&quot]. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 1 (7): 607–10. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]17409926[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]11. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Ranges estimated from quantile regression as shown in table 4 in: Friedrich, N; Alte, D; Volzke, H; Spilckeliss, E; Ludemann, J; Lerch, M; Kohlmann, T; Nauck, M et al. (2008). "Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: Results of the Study of Health in Pomerania (SHIP)". Growth Hormone & IGF Research 18 (3): 228–237. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1016/j.ghir.2007.09.005[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]17997337[/FONT][FONT=&quot].[/FONT][FONT=&quot]edit[/FONT]
[FONT=&quot]12. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Rosenbloom AL (August 2007). "The role of recombinant insulin-like growth factor I in the treatment of the short child". Curr. Opin. Pediatr. 19 (4): 458–64. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1097/MOP.0b013e3282094126[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]17630612[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]13. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Pollack A (2007-02-17). [/FONT][FONT=&quot]"Growth Drug Is Caught Up in Patent Fight"[/FONT][FONT=&quot]. The New York Times. Retrieved 2010-03-28.[/FONT]
[FONT=&quot]14. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Pollack A (2007-03-07). [/FONT][FONT=&quot]"To Settle Suit, Maker Agrees to Withdraw Growth Drug"[/FONT][FONT=&quot]. The New York Times. Retrieved 2010-03-28.[/FONT]
[FONT=&quot]15. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML (November 2008). "Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial". Neurology 71 (21): 1702–8. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1212/01.wnl.0000335163.88054.e7[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]19015485[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]16. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Sorenson EJ, Windbank AJ, Mandrekar JN, Bamlet WR, Appel SH, Armon C, Barkhaus PE, Bosch P, Boylan K, David WS, Feldman E, Glass J, Gutmann L, Katz J, King W, Luciano CA, McCluskey LF, Nash S, Newman DS, Pascuzzi RM, Pioro E, Sams LJ, Scelsa S, Simpson EP, Subramony SH, Tiryaki E, Thornton CA (November 2008). [/FONT][FONT=&quot]"Subcutaneous IGF-1 is not beneficial in 2-year ALS trial"[/FONT][FONT=&quot]. Neurology 71 (22): 1770–5. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1212/01.wnl.0000335970.78664.36[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMC[/FONT][FONT=&quot]2617770[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]19029516[/FONT][FONT=&quot]. [/FONT][FONT=&quot]Lay summary[/FONT][FONT=&quot] – newswise.com.[/FONT]
[FONT=&quot]17. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Fletcher L, Kohli S, Sprague SM, Scranton RA, Lipton SA, Parra A, Jimenez DF, Digicaylioglu M (July 2009). "Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke. Laboratory investigation". J. Neurosurg. 111 (1): 164–70. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.3171/2009.2.JNS081199[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]19284235[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]18. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Horton JK, Thimmaiah KN, Houghton JA, Horowitz ME, Houghton PJ (June 1989). "Modulation by verapamil of vincristine pharmacokinetics and toxicity in mice bearing human tumor xenografts". Biochem. Pharmacol. 38 (11): 1727–36. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1016/0006-2952(89)90405-X[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]2735930[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]19. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Ueki I, Ooi GT, Tremblay ML, Hurst KR, Bach LA, Boisclair YR (June 2000). [/FONT][FONT=&quot]"Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system"[/FONT][FONT=&quot]. Proc. Natl. Acad. Sci. U.S.A. 97 (12): 6868–73. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1073/pnas.120172697[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMC[/FONT][FONT=&quot]18767[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]10823924[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]20. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Buckway CK, Wilson EM, Ahlsén M, Bang P, Oh Y, Rosenfeld RG (October 2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". J. Clin. Endocrinol. Metab. 86 (10): 4943–50. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1210/jc.86.10.4943[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]11600567[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]21. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Cohen P, Graves HC, Peehl DM, Kamarei M, Giudice LC, Rosenfeld RG (October 1992). "Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma". J. Clin. Endocrinol. Metab. 75 (4): 1046–53. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1210/jc.75.4.1046[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]1383255[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]22. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Twigg SM, Baxter RC (March 1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". J. Biol. Chem. 273 (11): 6074–9. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1074/jbc.273.11.6074[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]9497324[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]23. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Firth SM, Ganeshprasad U, Baxter RC (January 1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". J. Biol. Chem. 273 (5): 2631–8. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1074/jbc.273.5.2631[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]9446566[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]24. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Bach LA, Hsieh S, Sakano K, Fujiwara H, Perdue JF, Rechler MM (May 1993). "Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6". J. Biol. Chem. 268 (13): 9246–54. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]7683646[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]25. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Qin X, Strong DD, Baylink DJ, Mohan S (September 1998). "Structure-function analysis of the human insulin-like growth factor binding protein-4". J. Biol. Chem. 273 (36): 23509–16. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1074/jbc.273.36.23509[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]9722589[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]26. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Ahmed S, Yamamoto K, Sato Y, Ogawa T, Herrmann A, Higashi S, Miyazaki K (October 2003). "Proteolytic processing of IGFBP-related protein-1 (TAF/angiomodulin/mac25) modulates its biological activity". Biochem. Biophys. Res. Commun. 310 (2): 612–8. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1016/j.bbrc.2003.09.058[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]14521955[/FONT][FONT=&quot].[/FONT]
[FONT=&quot]27. [/FONT][FONT=&quot]^[/FONT][FONT=&quot] Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG (November 1996). "Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II". J. Biol. Chem. 271 (48): 30322–5. [/FONT][FONT=&quot]doi[/FONT][FONT=&quot]:[/FONT][FONT=&quot]10.1074/jbc.271.48.30322[/FONT][FONT=&quot]. [/FONT][FONT=&quot]PMID[/FONT][FONT=&quot]8939990[/FONT][FONT=&quot].[/FONT]
[FONT=&quot][[/FONT][FONT=&quot]edit[/FONT][FONT=&quot]] Further reading[/FONT]


[FONT=&quot]IGF stands for insulin-like growth factor. Insulin-like growth factor 1 (IGF-1) is a polypeptide protein hormone similar in molecular structure to insulin . It plays an important role in childhood growth and continues to have effects in adults. It is a natural substance that is produced in the human body and is at its highest natural levels during puberty. During puberty IGF is the most responsible for the natural muscle growth that occurs during these few years. There are many different things that IGF does in the human body. Among the effects the most positive are increased amino acid transport to cells, increased glucose transport, increased protein synthesis, decreased protein degradation, and increased RNA synthesis. [/FONT]
clip_image012.gif
[FONT=&quot]Long R3 IGF-1 is signifacantly more potent than IGF-1. The enhanced potency is due to the decreased binding of Long R3 IGF-1 to all known IGF binding proteins. These binding proteins normally inhibit the biological actions of IGF's. When IGF is active it behaves differently in different types of tissues. In muscle cells proteins and associated cell components are stimulated. Protein synthesis is increased along with amino acid absorption. As a source of energy, IGF mobilizes fat for use as energy in adipose tissue. In lean tissue,

IGF prevents insulin from transporting glucose across cell membranes. As a result the cells have to switch to burning off fat as a source of energy.[/FONT]
[FONT=&quot]IGF also mimic's insulin in the human body. It makes muscles more sensitive to insulin's effects, so if you are a person that currently uses insulin you can lower your dosage by a decent margin to achieve the same effects, and as mentioned IGF will keep the insulin from making you fat. [/FONT]
[FONT=&quot]The most effective form of IGF is Long R3 IGF-1, it has been chemically altered and has had amino acid changes which cause it to avoid binding to proteins in the human body and allow it to have a much longer half life, around 20-30 hours. "Long R3 IGF-1 is an 83 amino acid analog of IGF-1 comprising the complete human IGF-1 sequence with the substition of an Arg(R) for the Glu(E) at position three, hence R3, and a 13 amino acid extension peptide at the N terminus. This analog of IGF-1 has been produced with the purpose of increasing the biological activity of the IGF peptide."[/FONT]
[FONT=&quot]IGF Cycles[/FONT]
[FONT=&quot]The most effective length for a cycle of IGF is 50 days on and 20-40 days off. The most controversy surrounding Long R3 IGF-1 is the effective dosage.[/FONT]
[FONT=&quot]IGF Dosage[/FONT]
[FONT=&quot]The most used dosages range between 20mcg/day to 120+mcg/day. IGF is only available by the milligram, one mg will give you a 50 day cycle at 20mcg/day, 2mg will give you a 50 day cycle at 40mcg/day, 3mg will give you a 50 day cycle at 60mcg/day, 4mg will give you a 50 day cycle at 80mcg/day and so on. The dosage issue mainly revolves around how much money you have to spend, plenty of people use the minimum dosage of 20mcg/day and are happy with the results. IGF is most effective when administered subcutaneous and injected once or twice daily at your current dosage. The best time for injections is either in the morning and/or immediately after weight training (if used for body building).[/FONT]
[FONT=&quot]IGF Effects and Results[/FONT]
[FONT=&quot]Perhaps the most interesting and potent effect IGF has on the human body is its ability to cause hyperplasia, which is an actual splitting of cells. Hypertrophy is what occurs during weight training and steroid use, it is simply an increase in the size of muscle cells. See, after puberty you have a set number of muscle cells, and all you are able to do is increase the size of these muscle cells, you don't actually gain more. But, with IGF use you are able to cause this hyperplasia which actually increases the number of muscle cells present in the tissue. So in a way IGF can actually change your genetic capabilities in terms of muscle tissue and cell count. IGF proliferates and differentiates the number of types of cells present. At a genetic level it has the potential to alter an individuals capacity to build superior muscle density and size.

Another frequently asked question of IGF refers to the real world results. With an effective dosage you can expect to gain 1-2 lbs of new lean muscle tissue every 2-3 weeks. Increased vascularity is also very common, people report seeing veins appear where they never have before. [/FONT]
[FONT=&quot]Overall, IGF is a very exciting drug due to its ability to alter ones genetic capabilities.[/FONT]



[FONT=&quot]Beginner’s Guide To IGF1-lr3[/FONT]
[FONT=&quot]The goal of this guide is to help both those that have not used IGF-1lr3 before and for those that simply would like a methodical approach to the “mechanics” of running it. This guide does not expand on the biochemistry of IGF-1, aside from a very simple introduction to it. I suggest reading a book or searching forums to educate yourself about the biochemistry of “peptides” or “IGF” if you require in-depth knowledge.

I am not a physician, thus cannot and do not diagnose ailments or diseases and/or nor do I suggest that IGF-1 is a remedy for any illness or diseases. IGF-1 should be treated with much respect. It is research compound, thus you should use at your own risk.

Currently (05/31/2008), in the United States, IGF-1lr3 is a research compound. It is legal to own this substance to the best of my knowledge (at current time). I am not an attorney, so please review your local law(s) regarding possession and administration of this therapeutic protein.

I do not condone the usage of IGF-1lr3 unless you are qualified to do so. This guide is provided as a research & development tool only.

IGF-1lr3 Overivew

Background:
Long Arg3 Insulin-like Growth Factor-I (Long-R3-IGF-I) is an 83 amino acid analog of IGF-I comprising the complete IGF-I sequence with the substitution of an Arg for the Glu at position 3 (hence R3), and a 13 amino acid extension peptide at the N-terminus. Long-R3-IGF-I is significantly more potent than IGF-I in vitro. The enhanced potency is due to the markedly decreased binding of Long-R3-IGF-I to IGF binding proteins which normally inhibit the biological actions of IGFs.



Description:
Recombinant Human Long-R3-IGF-I produced in E. coli is a single, non-glycosylated, polypeptide chain containing 83 amino acids and having a molecular mass of 9111 Dalton.



0.6% Acetic Acid Overview
Acetic Acid (AA) will be used to reconstitute (turn your lyophilized IGF-1 into a liquid form) your IGF-1. The standard is to use 0.6% AA. This concentration is typically not available for you to purchase. You can make your own 0.6% AA and I will show you how below (many have used this method successfully).

Making 0.6% Acetic Acid
You will have to purchase a few items upfront. Here is a “grocery list” of items you will need. I have provided check boxes for you to check off once you have purchased these items.

Items Needed:
• Distilled white vinegar (grocery store)
• Distilled water (grocery store)
• 0.2-0.22um sterile Whatman syringe filter
• 10mL syringe with a luer lock tip
• ~20-22 gauge needles (just the needles)
• Sterile glass vial (10-20mL)
• Alcohol prep pads – sterile kind (70% isopropyl alcohol)


Quick Guide:
1. Swab the top of your sterile vial with alcohol prep pad (70% isopropyl alcohol)
2. Mix 7.5mL distilled water with 1.0mL vinegar
3. Add Whatman syringe filter
4. Add sterile ~20ga. needle to end of Whatman filter
5. Inject the 8.5mL of solution into the sterile vial
6. You now have sterile 0.6% acetic acid



Detailed Directions:
1. Wash you hands thoroughly
2. Optional: wear alcohol treated exam gloves (rub your gloved hands together with 70% isopropyl alcohol on them until dry)
3. Using a sterile alcohol prep pad, swab the top of your sterile glass vial (into which the acetic acid solution will be held in)
4. Using the 10mL syringe with a ~20ga. needle on the end, draw up 7.5mL distilled water
5. Using the same syringe, now draw up 1mL vinegar
6. Remove needle from the syringe and discard
7. Attach 0.2-0.22um Whatman sterile syringe filter (do not touch the free end that will have a needle on it)
8. Put a new, sterile needle (~20 gauge) onto the free end of the Whatman filter (do not touch needle)
a. Do not use the same needle on the Whatman that was used to originally draw up the unsterile vinegar and distilled water.
9. Put a ~20 gauge sterile needle into the top of your sterile glass vial to act as a vent
10. Inject the acetic acid solution into the vial
11. You are now done and should have sterile 0.6% acetic acid

Notes:
1. These items MUST be sterile: 20-22ga. Needles, whatman filter, glass vial
2. Whatman filter: These small, sterile filters are used to filter the acetic acid solution so it is sterile. It does not matter that the liquid in your syringe (distilled water & vinegar) is not sterile, nor does it matter that the syringe itself is not sterile. Once the liquid goes through the filter it is STERILE. Thus, everything after the filter must be sterile!
3. You will most likely use 1mL (milliliter) of 0.6% AA to reconstitute your IGF-1. Thus, you should make at least 1.5mL. In reality, it’s just as easy to make 8.5mL as I have stated in the above directions. You will have plenty for use later then.
4. Do NOT reuse the Whatman filter nor any needles! Discard immediately.




Reconstituting IGF-1lr3
Reconstitution is simply the addition of the 0.6% AA to your lyophilized IGF-1.
Assumption: 1mg/mL IGF-1/AA (1mg IGF-1 will be combined with 1mL AA; 1mg IGF-1 is the same as 1,000mcg)

1. Swab the top of your IGF-1 vial with a sterile alcohol prep pad
2. Swab the top of your 0.6% AA vial with a sterile alcohol prep pad
3. Using either multiple insulin syringe volumes (example: 2 x 0.5cc) or a single large syringe, obtain 1.0mL of 0.6% AA.
4. In the IGF-1 vial, insert a sterile ~20 ga. needle to act as a vent
5. Inject the 1.0mL of AA very slowly and dribble it down the side of the vial.
a. Be very careful with this peptide as it is very delicate!
6. Remove the needle & syringe and discard
7. Gently swirl the vial or roll between your hands.
a. Again, be very gentle here
8. You now have 1mg/mL of IGF-1
a. This is the same as: 1,000mcg/mL

Notes:
1. If you added 2mL of AA, it would be a 0.5mg/mL
2. I have an Excel calculator that will help you with these calculation.


Injecting IGF-1lr3
If this is your first time with injections, don’t worry. You will be using a very fine gauge insulin syringe which means you will most likely have nearly effortless injections. These things are so tiny and sharp you may not even feel it penetrating. If you use sterile procedure, aspirate prior to injection, and have diluted your IGF-1/AA solution with enough bacteriostatic water (BW), you should have no issues with your injections and very minimal post-injection discomfort (if any at all!).

I cannot stress enough the importance on two topics: A) sterility, and B) pre-injection aspiration. Always swab the injection site(s) with a sterile isopropyl alcohol (IPA) pad and aspirate prior to injecting the IGF-1. No questions asked!

You will most likely intramuscular (IM) injections, but subcutaneous (sub-q) injections are also followed by some, but current theory is that IM will yield a localized effect. By “localized effect”, I am referring to the effect IGF-1 will have at the injection site. So if you inject IM into biceps, it is thought that your bicep muscles will get more of a dose of IGF-1 than other parts of your body (some which you don’t want to be effected, such as the intestines). Both types of injections will have systemic effects (affecting the body as a whole). Long R3 IGF-1 has an estimated half-life of 20-30hrs (taken from IGTROPIN data).

This guide assumes you will be doing bilateral IM injections. More below.

Bilateral injections are injections that are evenly divided between two muscles. If you are injecting 40mcg (micrograms) bilaterally, you will be injecting 20mcg into the right bicep and 20mcg into the left bicep.

Current theorized best practice is to you inject your peptide post workout (PWO). You have a small window of optimal opportunity. Ideally, you would inject immediately PWO, but some do not like the idea of injecting in a public location, such as the gym. Your next best option is to make your way home ASAP and have your needles loaded and ready (with your alcohol swabs sitting near by).


Sterility
Without a doubt, sterility is a major concern with injections. You have to be conscious of bacteria and other infectious agents at all times when performing injections or other procedures that require sterility (such as reconstitutions and making 0.6% AA).

Bacteria (and viruses, and spores, etc) are invisible to the naked eye. Yet they are everywhere. It is very important that you acquire sterile alcohol prep pads (make sure it says “sterile” before you buy them). They are extremely cheap and effective.

Wash your hands! Before attempting anything requiring sterile technique, wash your hands and dry them with a clean paper towel (not the dirty towel hanging in the bathroom!). For optimal sterility, you may purchase exam gloves (latex or non-latex) and, after putting them on, you can dump some isopropyl alcohol (IPA) onto them and rub your hands together thoroughly. Now you really have sterile hands. Exam gloves are very inexpensive as is the bottle of IPA. IPA can be purchased for ~$1/bottle in the grocery store where the band-aids and whatnot.

I recommend you use a fresh syringe for each injection. Yes, some choose to use one syringe, but my feeling is that the syringes are so inexpensive and the risk of cross-contamination from one injection site to the other isn’t worth the risk. Furthermore, every time your syringe needle has to penetrate something (rubber stoppers in vials, skin, etc) it dulls the tip. Thus, maximum comfort is also achieved with fresh syringes.

This topic of “one or two syringes” can be argued, but if it’s your first time, play it safe and get off to a great start by using 2!

Pre-injection Aspiration
Pre-injection aspiration is what you do after the needle has penetrated the muscle. You must gently and slightly pull back on the needle’s plunger to see if you have hit a vein/artery.

Either of two things will happen upon aspiration: A) bubbles/air and/or clear liquid will appear in the syringe (this is good), or B) blood will appear (bad).

If A) occurs, proceed with your injection. If B) occurs, then simply withdraw the needle, and re-pin a different location in that same muscle. You do NOT want to inject your solution into a vein/artery! This may result in very serious consequences. Don’t worry, you can avoid this by simply aspirating slightly. Have faith in yourself.

Injection Procedure
First, do not get all worked up over injecting IGF-1. Easier said than done, I know. But the reality is, the insulin syringes are extremely gentle. Also, millions of people around the world, including women and children, use these syringes daily to treat Diabetes. So you know it can’t be that bad (seriously)! I highly recommend watching a couple videos on youtube regarding intramuscular (IM) injections to get a general idea of how they’re done if you’ve never witnessed them!

Back-Loading With Bacteriostatic Water (BW)
Back-loading is a process in which you dilute the IGF-1/AA solution that is in your syringe. The point is to dilute the acidity to a point that it will no longer cause tissue necrosis (death/damage) or pain upon injection. It is recommended to dilute no less than 4:1 (4 parts BW to 1 part IGF-1/AA).

Example: If you are injecting 40mcg bilat, IM, you will have two syringes each with 20mcg IGF-1. Assume you want to draw 2 IU IGF-1. You will draw 2 IUs of the IGF-1/AA solution, then draw 2x4 = 8 IUs of BW (four times the amount of IGF-1/AA solution). The total number of IUs in each syringe will be 2 + 8 = 10 IUs. It will not hurt you if you decide to back-load with more BW. It is a personal preference.

***Use my Excel-based “IGF-1” calculator to determine how many IUs you will need for a particular insulin syringe (1cc, 0.5cc, 0.3cc).

Recommended Best Injection Method: Injecting bilaterally, post workout, intramuscularly (Bilat, PWO, IM)



Items you will need
1. Alcohol prep pads
2. 2 insulin syringes
3. Bacteriostatic water (BW)
4. Optional: exam gloves
5. Optional: IPA (to rub gloves with and to clean the surrounding area)

Injection Directions
1. Wash your hands thoroughly
2. Optional: put on exam gloves and rub with IPA until dry
3. Using an alcohol swab, clean the tops of both the IGF-1 vial and the BW vial.
4. Using a fresh alcohol swab, thoroughly clean the injection sites (let dry)
5. Fill each syringe with the appropriate amount of IGF-1/AA solution
a. Do NOT touch the needles to anything but sterile surfaces!
b. It is recommended that you clean/sanitize the area/surfaces you’re working in, in case you mindlessly touch a needle to a table (or other area).
6. Back-loading: Draw up the necessary amount of BW into each syringe.
a. Tilt the needle up and down so the bubble(s) rise and fall, which mixes the solution slightly
7. With the needle pointing up, flick the syringe body to get the bubbles to rise to the needle
8. Slowly expel the air; be careful to not quirt liquid out as this wastes IGF-1
a. It takes >3mL of air to cause harm; small volumes of accidentally injected air will most likely be absorbed by muscle tissue
9. Insert syringe and aspirate by slightly pulling up on the plunger to see if you have hit a vessel. If you see blood, remove needle, and try again (no need to change syringes). If you do NOT see blood, proceed to inject.
10. Perform “7.” thru “9” above on other side.
11. Discard sharps in appropriate container



Glossary

Acetic Acid (AA): An acid that, when diluted to 0.6%, will act as a preservative for your IGF-1. An off-the-shelf version of 5% AA is distilled white vinegar; your IGF-1 may be supplied in acetic acid (usually 0.6%)

Aspiration: The technique of checking to see if your inserted needle is in a blood vessel. It is performed by gently pulling up on the syringe plunger until you either see bubbles/air/clear liquid, or blood. If you see blood, remove needle, and re-try the insertion.

Back-loading: The process of diluting your IGF-1/AA with bacteriostatic water, prior to injection. The purpose is to dilute the acidity of the AA so it doesn’t cause tissue damage and so it doesn’t cause injection burn/discomfort.
A. Draw desired amount of IGF-1/AA solution
B. Back-load with BW: draw desired amount of BW

Bacteriostatic Water (BW): This is water for injection (sterile) that has benzoyl alcohol (BA) added to it to ward of contamination. You use BW to dilute your IGF-1/AA solution prior to injection (aka, “back-loading”).

Bilateral Injection (bilat): An injection which involves the administration of IGF-1 in equal amounts to each side of the body. If you are injecting 40mcg IGF-1 into the biceps bilaterally, you will be injecting 20mcg into each bicep (left & right side).

Distilled Water: Has virtually all of its impurities removed through distillation. Distillation involves boiling the water and then condensing the steam into a clean cup, leaving nearly all of the solid contaminants behind. This is NOT sterile water. It can be purchased in any grocery store in the “water” isle.

Endogenous: Substances that originate from within an organism, tissue, or cell. It is the opposite of exogenous

Exogenous: Refers to an action or object coming from outside a system. It is the opposite of endogenous.

IM: Intramuscular; typically refers to the type of injection where you inject a substance directly into muscle tissue

IGF-1 lr3: A peptide that is responsible for new muscle tissue development; it is synthetic and has a much longer circulatory life than endogenous IGF-1

Lyophilized: The form in which IGF-1 is typically supplied; this is a freeze-dried protein which is performed in a vacuum; appearance may range from a fine, loose white powder, to a white solid “paste”-type substance

PWO: Post Work Out; refers to the time period when the administration of IGF-1 is thought to be the most effective (immediately PWO).

Reconstitution: The addition of 0.6% acetic acid to lyophilized IGF-1r3 to get it into solution. Typically one reconstitutes using 1mL or 2mL of acetic acid, yielding 1mg/mL or 2mg/mL of IGF-1/AA.

Sub-q: Subcutaneous; typically refers to the type of injection where you inject a substance under the skin; this results in systemic distribution of substances. [/FONT]
 
Appreciate it man but I'm not looking for wikipedia.........if I were I would have just gone there (and I have).

I'm looking for personal input, people who have seen their lab rats do these peptides and have a human response and opinion on the side effects and benefits.

And I have been researching, I'm not dumb. That's why I created this thread; there is plenty of hype out there on how awesome peptides are because there the new shit, but finding anything on their side effects other than great dookies and increased cortisol release has been more than challenging.

If you'll notice, the wiki articles also did not address sides other than cort production and desensitization (which isn't really a side effect....just a natural response to substance).......which was my point in the first place.
 
increased cortisol puts your body in a catabolic state (muscle breakdown) raises blood pressure and lowers potassium levels by increased absorption of sodium in the cells. i think a cortisol lowerer should be a part of any pct such as erase. cortisol is the direct counterpart to anabolism by yopur body to maintain homeostasis during times of high anabolic compounds in the body
 
Now that, sir, is helpful. Thank you for that.

What about during cycle? How can you keep cort production down while your lab rats are on?
 
just by being on cycle your cort should remain low due to the increase in anabolics. catabolism and anabolism are the exact opposites of each other and your body strives for homeostasis so i do believe u r fine while on, its going into pct and coming off where cort levels are raised. i have the alpha t2/erase/shift stack for a little extra fatloss im gonna run here soon, but im thinkin about getting a couple extra bottles of erase to try and run in pct to see how the body reacts to the cort suppression effect erase has, and if it makes any difference at all. might be a new staple in pct?!
 
Ghrp's make me hold water. That's a good point about the cortisol. I'm cutting, and I think the water retention and increased cortisol has kept me from dropping what I wanted to, in the time frame I wanted to do it in. But, between the peps and s4, I've had a dramatic recomp. The only other drawback is pinning 3x a day. That gets old after a couple months.
 
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