IGF-1 LR3

Native IGF-1 circulates roughly 99 percent bound to binding proteins (IGFBPs) and is thereby kept away from its receptor. IGF-1 LR3 was engineered to sidestep exactly that: arginine replaces glutamic acid at position 3, and 13 extra amino acids are attached at the N-terminus, 83 in total. Affinity for the IGFBPs drops by a factor of 100 to 1000 as a result.

What studies show:

• The Long IGF-I analogues, among them Long Arg3 IGF-I, acted more strongly on protein and DNA synthesis in myoblasts than native IGF-I; the explanation is their altered binding to the IGFBPs (1992).
• In rats pushed into a catabolic state with dexamethasone, LR3 was about 2.5 times more anabolic than native IGF-I even though it binds the receptor less tightly; the difference lies in its weak IGFBP binding (1992).
• Viral expression of IGF-I in skeletal muscle increased muscle mass in the classic work by Barton-Davis (1998).
• IGF-1-driven hypertrophy of myotubes runs through PI3K, Akt and mTOR (Rommel 2001).

The consequence of the modifications: instead of a few minutes, the analog stays available for 20 to 30 hours in research models. At the IGF-1 receptor it primarily fires the PI3K/Akt/mTOR pathway, the central mediator of anabolic effects, and secondarily the MAPK/ERK pathway for proliferation and differentiation. Muscle models describe satellite cell activation, increased protein synthesis and fibre hypertrophy. LR3 is used in research on hypertrophy, sarcopenia, regeneration and tissue engineering, wherever isolated receptor activation free of IGFBP influence is the question.

Direct receptor activation that is independent of the binding proteins, together with the long duration of action, calls for more attention than pure GH secretagogues do.

• Low blood sugar is the main point: IGF-1 acts like insulin, and the literature lists sweating, shaking and grogginess as signs of hypoglycemia.
• Because the activated pathways (PI3K/Akt/mTOR) are proliferative, there is a theoretical debate about whether existing abnormal tissue might grow along. No evidence supports it; the point remains open.
• Injection site: redness, pressure, brief irritation.
• Transient fluid retention, occasional and dose-dependent.
• Human data over long periods are missing; the basis is animal and cell models.

This summary is no substitute for medical advice.

• Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats - LR3 versus native IGF-I in a catabolic rat model.
• Viral mediated expression of IGF-I in skeletal muscle - classic work on IGF-I and muscle mass.
• Mediation of IGF-1-induced skeletal myotube hypertrophy by PI3K/Akt/mTOR - the signalling route behind myotube hypertrophy.