IGF-1 LR3

Muscle Growth & Anabolic Activity

• Stimulates muscle protein synthesis via activation of the PI3K/Akt/mTOR pathway.
• Suppresses muscle protein breakdown by inhibiting the FoxO-ubiquitin-proteasome system.
• Enhances muscle fiber hypertrophy and strength in rodent models.
• Activates satellite cells, promoting regeneration and repair of damaged muscle tissue.

Tissue Regeneration & Wound Healing

• Accelerates re-epithelialization and collagen formation in dermal wound models.
• Promotes intestinal epithelial growth, villus expansion, and mucosal cellularity.
• Supports stem cell recruitment and differentiation in muscle, gut, and cardiac tissue.
• Enhances tissue repair in estrogen-deficient or metabolically compromised research models.

Glucose Metabolism & Insulin Sensitivity

• Increases glucose uptake in adipocytes and myocytes through GLUT4 translocation.
• Exerts insulin-like effects on energy storage, nutrient delivery, and glycemic balance.
• Lowers circulating insulin and blood glucose in calorie-restricted rodent studies.
• May enhance insulin sensitivity and metabolic flexibility in co-treatment research.

Lipid Metabolism & Nutrient Partitioning

• Reduces fat mass in preclinical models through nutrient repartitioning.
• Enhances fatty acid oxidation and preserves lean mass under energy deficit.
• Decreases carcass adiposity in tumor-bearing cachexia studies.
• Shifts metabolic balance toward protein retention and lipid utilization.

Neuroprotection & Brain Energy Support

• Supports neuronal survival, neurite growth, and synaptic plasticity.
• Reduces hippocampal mitochondrial dysfunction in high-fat diet models.
• Activates CREB/PGC-1α pathways to enhance neuroenergetic output.
• Protects against ischemic brain injury and promotes post-injury recovery.

Cardiovascular Repair & Vascular Stability

• Reduces atherosclerotic plaque volume and enhances fibrous cap thickness.
• Promotes smooth muscle cell stability and plaque integrity in ApoE⁻/⁻ models.
• Stimulates endothelial NO production and improves vascular function.
• Decreases cardiomyocyte apoptosis and enhances heart remodeling after infarction.

Cell Signaling & Growth Pathways

• Activates IGF-1 receptor to initiate PI3K/Akt and MAPK/ERK signaling cascades.
• Drives DNA synthesis, mitogenesis, and cellular differentiation in vitro.
• Resists IGF-binding protein (IGFBP) inhibition, increasing bioactive availability.
• Sustains long-duration receptor activation due to extended half-life.

Aging, Recovery & Muscle Preservation

• Preserves lean body mass under caloric restriction or disease stress.
• Enhances anabolic recovery in aging and injury-induced muscle loss.
• Improves nitrogen balance in protein-deprived research models.
• Supports cell regeneration in experimental aging and senescence pathways.

Oncogenic & Safety Considerations

• Stimulates proliferation of both healthy and malignant cells in tumor-bearing models.
• Increases nutrient flow to tumors in systemic cachexia settings.
• Requires caution in oncology-related experiments due to pro-growth signaling.
• Not approved for human use; for controlled preclinical laboratory investigation only.

To maximize the utility of IGF-1 LR3 in experimental models, researchers often combine it with synergistic compounds that enhance its anabolic, regenerative, metabolic, or neuroprotective activity. These combinations are used across studies exploring muscle growth, tissue recovery, metabolic modulation, cognitive function, and cell signaling.

Below is a summary of notable IGF-1 LR3 synergies validated in preclinical or mechanistic studies:

IGF-1 LR3 Synergistic Compounds

Potential Research Use Cases for IGF-1 LR3 Combinations

• Muscle Growth & Hypertrophy Models:
  IGF-1 LR3 + CJC-1295 (No DAC) / Ipamorelin / TB-500
• Tendon, Ligament & Joint Repair:
  IGF-1 LR3 + BPC-157 / TB-500
  
• Skin & Connective-Tissue Regeneration:
  IGF-1 LR3 + GHK-Cu / Glutathione
  
• Metabolic & Mitochondrial Research:
  IGF-1 LR3 + NAD⁺ / MOTS-C
  
• Systemic Recovery & Immune Balance:
  IGF-1 LR3 + Thymosin Alpha-1 / CJC-1295 (DAC)
  
  

IGF-1 LR3 is a synthetic analog of insulin-like growth factor-1 (IGF-1) engineered for extended activity and potency. It differs from native IGF-1 by an arginine substitution at the 3rd amino acid and a 13-amino-acid extension at the N-terminus, modifications that confer a significantly longer half-life, much lower IGF-binding protein affinity, and roughly 3-fold greater potency in vivo (Ref. 1).

Anabolic Effects (Muscle Growth)

• Muscle Protein Synthesis and Anti-Catabolic Action: IGF-1 is a key regulator of skeletal muscle anabolism. It increases muscle protein synthesis via activation of the PI3K/Akt/mTOR pathway and suppresses proteolysis by inhibiting FoxO-mediated ubiquitin–proteasome activity (Ref. 2).
• Hypertrophy and Strength Gains: Preclinical experiments have shown that IGF-1 promotes muscle mass and strength development, reduces muscle fiber degeneration, and increases the proliferative capacity of muscle satellite cells. For example, IGF-1 activation of Akt/mTOR signaling drives hypertrophy, and local IGF-1 overexpression enhances fiber size and function with satellite cell involvement (Refs. 3, 4). IGF-1 LR3, with its prolonged activity, amplifies these anabolic effects in laboratory studies (Ref. 1).
• Nutrient Partitioning (Anti-Catabolic in Caloric Restriction): In rat models of food restriction, continuous infusion of IGF-1 analogs has been investigated for effects on body composition and nitrogen balance; LR3-IGF-1 alters fuel utilization and body composition under restriction (Ref. 5).
• Muscle Regeneration: IGF-1 plays a pivotal role in muscle repair by activating satellite cells (muscle stem cells). After injury, local IGF-1 stimulates satellite cell proliferation and differentiation into new fibers, facilitating regeneration; blocking satellite cell proliferation blunts IGF-1–induced hypertrophy (Ref. 4).

Regenerative and Healing Effects

• Intestinal Growth and Repair: IGF-1 LR3 exhibits potent trophic effects on visceral tissues. In neonatal rats, dietary LR3-IGF-1 markedly increased small-intestinal villus height and epithelial cell counts versus unsupplemented controls (Ref. 7). Continuous administration of LR3-IGF-1 in rodents also produced robust mucosal growth responses in gut tissues compared with native IGF-1 (Ref. 6).
• Wound Healing: IGF-1 supports dermal repair. In estrogen-deficient (ovariectomized) mice, exogenous IGF-1 improved wound healing by modulating local inflammation and promoting re-epithelialization (Ref. 8).
  
• Stem Cell Activation: The mechano-growth factor (MGF/IGF-1 Ec) isoform is upregulated after muscle damage and shows neuroprotective and progenitor-activating properties in experimental models (Ref. 9).

Metabolic Effects

• Insulin-Like Activity: Due to overlap of IGF-1 and insulin signaling, IGF-1 can promote glucose uptake in adipocytes and myocytes. Dose-dependent stimulation of glucose uptake by IGF-1 (including LR3-IGF-1 in comparative assays) has been demonstrated in cultured adipocytes (Ref. 12).
• Effects on Blood Sugar and Fat Metabolism: In vivo, IGF-1 administration can lower circulating insulin and influence glucose handling, consistent with insulin-like activity; IGF-1 analog infusion during energy restriction modifies metabolic readouts and body composition in rodents (Ref. 5).
• Protein & Lipid Metabolism: IGF-1 signaling favors an anabolic profile—enhancing amino acid uptake and protein synthesis while limiting proteolysis—and has tissue-specific effects in adipose. In a tumor-bearing rat model, LR3-IGF-1 alone reduced carcass fat while altering systemic metabolism; combined insulin co-administration changed nutrient partitioning and blunted tumor growth acceleration (Ref. 14).

Neurological Effects (Neuroprotection)

• Neurotrophic and Neuroprotective Actions: IGF-1 is neurotrophic in central and peripheral nervous systems and can protect neurons under stress. An IGF-1 splice variant peptide (MGF C-terminal) showed strong neuroprotection in ischemia models (Ref. 9).
• Mood and Cognitive Function: In high-fat diet mouse models, PEG-IGF-1 alleviated depression-like behaviors and hippocampal mitochondrial dysfunction via activation of CREB/PGC-1α signaling (Ref. 13).

Cardiovascular Effects

• Atherosclerosis and Vascular Health: In ApoE-knockout mice, treatment with Long R3 IGF-1 significantly reduced atherosclerotic plaque burden and improved features of plaque stability (Ref. 11).
  
• Cardiac Tissue and Blood Vessels: IGF-1 promotes nitric oxide (NO) generation in vascular endothelium/vascular tissue, supporting vasodilation and endothelial function (Ref. 10).

Cellular Signaling Mechanisms

• Receptor Binding and Pathways: IGF-1 LR3 acts via IGF-1R to activate PI3K/Akt and MAPK/ERK cascades that mediate hypertrophy and cell survival (Refs. 2, 3).
  
• Enhanced Bioavailability (IGFBP Evasion): LR3’s reduced affinity for IGF-binding proteins increases its unbound, bioactive fraction and functional half-life compared with native IGF-1 (Ref. 1).
• Cell Proliferation and Differentiation: IGF-1 is a potent mitogen in many cell types; LR3-IGF-1 displays greater mitogenic/functional potency than native IGF-1 in several in vivo and in vitro models (Ref. 1).

Oncogenic Activity and Safety Observations

• Mitogenic Effects in Tumor Models: In tumor-bearing rats, LR3-IGF-1 infusion increased growth of pre-existing mammary tumors via systemic effects; co-administration of insulin altered intake/partitioning and attenuated the tumor growth acceleration (Ref. 14).
• No Human or Clinical Use: IGF-1 LR3 is not approved for therapeutic use in humans and remains restricted to preclinical research.