Optimization of IGF-I for therapeutic applications in skeletal muscle

Source: Collective analysis of published data from the Journal of Endocrinology , Growth Hormone & IGF Research , and pharmacokinetic reports of Long R3 IGF-1


Purpose of the study

To characterize the pharmacological profile of IGF-1 LR3 – a long-acting analogue of human insulin-like growth factor 1 (IGF-I) – in order to determine its potential for studies on muscle growth, metabolism and cell differentiation.

IGF-1 LR3 (Long R3 IGF-I) is a modified peptide in which the glutamic acid at position 3 has been replaced with arginine and the N-terminus has been extended by 13 amino acids. These modifications significantly reduce its binding to IGF-binding proteins (IGFBPs), increasing its bioavailability and duration of action.


Study design

  • Type: preclinical in vitro and in vivo studies

  • Models: myoblast cell lines, rodents and primates

  • Interventions: systemic or topical administration of IGF-1 LR3

  • Parameters assessed: cell proliferation, protein synthesis, IGF-1R phosphorylation, insulin sensitivity


Main results

Pharmacokinetics

  • IGF-1 LR3 has an extended half-life (~20–30 hours) compared to endogenous IGF-I (~10–15 min).

  • Reduced binding to IGFBPs → greater free fraction and access to IGF-1 receptors.

  • Increased stability in plasma and longer anabolic signal.

Cellular and tissue effects

  • Stimulates phosphorylation of IGF-1R and the PI3K/Akt pathway, leading to enhanced protein synthesis and cell growth.

  • Increases myoblast proliferation and activates satellite cells in animal models.

  • Maintains an anabolic state without the need for frequent application.

Metabolic effects

  • Moderately increases glucose uptake in muscles, but with lower hypoglycemic activity compared to insulin.

  • Promotes lipolysis and improves insulin sensitivity in experimental models.


Conclusions

  • IGF-1 LR3 is a long-acting analog with increased biological activity and reduced binding to IGFBPs.

  • Maintains a stable anabolic effect and stimulates muscle growth in experimental models.

  • Suitable for research purposes related to muscle regeneration, metabolic diseases and cell signaling.


Practical importance

  • IGF-1 LR3 is a valuable tool for studying anabolic mechanisms and the role of IGF-1 in muscle homeostasis.

  • Requires caution when dosing in preclinical models due to potential effects on cell proliferation and glucose metabolism.