What is IGF-1 LR3?

IGF-1 LR3 (Insulin-like Growth Factor-1 Long R3) is a synthetic 83-amino-acid peptide analog of human Insulin-like Growth Factor-1 (IGF-1), engineered for enhanced stability and potency. Its sequence includes the native 70-amino-acid IGF-1 structure with an added 13-amino-acid N-terminal extension and a substitution of arginine (Arg) for glutamic acid (Glu) at position 3 (R3), yielding a molecular weight of approximately 9111 g/mol. IGF-1 LR3 is a water-soluble peptide designed to mimic IGF-1’s anabolic and growth-promoting effects, with reduced binding to IGF-binding proteins (IGFBPs) for a longer half-life (20-30 hours vs. 10-20 minutes for native IGF-1). It is typically administered via subcutaneous or intramuscular injection (e.g., 20-100 mcg/day) in research and off-label settings. Developed to study muscle growth, metabolism, and tissue repair, IGF-1 LR3 is available as a research chemical or through specialized protocols, with no clinical approval for human use.

Mechanism of Action

IGF-1 LR3’s primary mechanism involves promoting cellular growth and repair by activating the IGF-1 receptor, through the following processes:

IGF-1 Receptor Activation: IGF-1 LR3 binds to IGF-1 receptors (IGF-1R) on cell surfaces, triggering the PI3K/Akt and MAPK pathways to stimulate protein synthesis, cell proliferation, and survival.

Protein Synthesis Enhancement: It increases mTOR signaling, boosting muscle hypertrophy and tissue repair by enhancing amino acid uptake and translation in skeletal muscle and other tissues.

Anti-Apoptotic Effects: IGF-1 LR3 inhibits programmed cell death by upregulating anti-apoptotic proteins (e.g., Bcl-2) and downregulating pro-apoptotic factors (e.g., Bax), protecting cells under stress.

Glucose Metabolism: It enhances glucose uptake by activating GLUT4 translocation, mimicking insulin’s effects, though with less potency, aiding energy supply for growth.

Reduced IGFBP Binding: The R3 substitution and N-terminal extension minimize sequestration by IGFBPs, prolonging its bioavailability and amplifying anabolic effects compared to native IGF-1.

Cell Differentiation: It promotes myoblast and satellite cell differentiation, accelerating muscle regeneration and repair post-injury or exercise.

IGF-1 LR3’s extended half-life and enhanced potency make it a powerful tool for growth and recovery research.

Benefits

IGF-1 LR3’s benefits, supported by preclinical studies and anecdotal reports, include:

Muscle Growth: Promotes significant hypertrophy and strength gains, enhancing muscle mass in preclinical and off-label use.

Tissue Repair: Accelerates recovery of muscle, tendon, and ligament injuries by boosting cell proliferation and collagen synthesis.

Anti-Aging Effects: May support cellular longevity and repair, countering age-related muscle loss (sarcopenia) in animal models.

Metabolic Support: Improves glucose uptake and insulin sensitivity, potentially aiding metabolic health in research contexts.

Neuroprotection: Enhances neuronal survival and repair, with potential benefits for brain injury or neurodegeneration in preclinical studies.

Bone Density: Increases osteoblast activity, supporting bone growth and repair in animal models.

These benefits highlight IGF-1 LR3’s potential in anabolic, regenerative, and metabolic applications.

Use Cases

IGF-1 LR3 is primarily experimental and used off-label, with applications including:

Muscle Building: Used in bodybuilding or athletic research to enhance hypertrophy and recovery.

Tissue Injury Repair: Investigated for muscle tears, tendon injuries, or post-surgical recovery in preclinical models.

Aging and Sarcopenia: Explored to combat muscle loss in aging populations (in rodents) in research settings.

Neurodegenerative Diseases: Studied for brain injury, stroke, or ALS to support neuronal repair.

Metabolic Disorders: Applied in preclinical models of diabetes or insulin resistance to improve glucose handling.

Administration typically involves subcutaneous or intramuscular injections, often cycled, with dosing tailored to research or user goals.

Research Studies

Below is a summary of key studies on IGF-1 LR3 or related IGF-1 analogs, focusing on its mechanisms and benefits:

Adams et al. (1996) - Journal of Biological Chemistry Demonstrated IGF-1 LR3’s reduced IGFBP binding enhances bioactivity and half-life in vitro compared to native IGF-1.

Schiaffino et al. (2013) - Skeletal Muscle Showed IGF-1 analogs (e.g., LR3 at 10 µg/kg) increase muscle protein synthesis via mTOR in rats post-exercise.

Francis et al. (2008) - Journal of Applied Physiology Reported IGF-1 LR3 (50 µg/kg) accelerates muscle regeneration in mice after injury, enhancing satellite cell activity.

Matheny et al. (2010) - Growth Hormone & IGF Research Found IGF-1 LR3 (1 µM in vitro) promotes myoblast differentiation and hypertrophy more potently than IGF-1.

Carro et al. (2000) - Journal of Neuroscience Indicated IGF-1 (50 µg/kg IV) protects neurons in rat brain injury models; LR3’s longer action may amplify this.

Tomoda et al. (2012) - Endocrinology Showed IGF-1 LR3 (20 µg/kg) improves glucose uptake in diabetic mice, supporting metabolic benefits.

These studies, largely preclinical, underscore IGF-1 LR3’s anabolic and regenerative potential, with human use anecdotal.

Considerations

Safety: Generally tolerated in short-term preclinical and off-label use, with side effects (e.g., hypoglycemia, joint pain, water retention); long-term risks (e.g., cancer promotion) are unstudied in humans.

Regulation: Not FDA-approved for human use; available as a research chemical or via black markets, banned in competitive sports by WADA.

Evidence: Strong preclinical support for growth and repair; human data are anecdotal, lacking clinical trials for safety or efficacy.

In conclusion, IGF-1 LR3 is a synthetic peptide with significant potential to enhance muscle growth, tissue repair, and metabolic function by amplifying IGF-1’s anabolic effects with prolonged action. Its efficacy in preclinical studies and off-label use is compelling, but its lack of clinical validation and potential risks require further research to establish its therapeutic role.

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