IGF-1LR3

Native IGF-1 Background

Native IGF-1 is a 70-amino acid polypeptide hormone structurally similar to insulin. It is a primary mediator of growth hormone's effects, involved in cellular growth, proliferation, and differentiation. Most circulating IGF-1 is bound to a family of IGF-binding proteins (IGFBPs), which regulate its bioavailability and half-life.

Structural Modifications

IGF-1 LR3 is an 83-amino acid polypeptide. It incorporates two modifications to the native IGF-1 sequence: an N-terminal extension of 13 amino acids, and the substitution of glutamic acid with arginine at position 3 (R3).

These modifications have been reported to reduce the binding affinity of IGF-1 LR3 for IGFBPs by approximately 100- to 1000-fold compared to native IGF-1. This results in a higher proportion of the peptide existing in a free state, available to interact with cell surface receptors.

Pharmacokinetic Properties

Due to its reduced binding to IGFBPs, IGF-1 LR3 has a distinct pharmacokinetic profile compared to native IGF-1. Its reported half-life in circulation is approximately 20-30 hours.

In vitro studies have reported that IGF-1 LR3 is more potent than native IGF-1 in stimulating processes like protein synthesis and cellular proliferation. It has been investigated in various research contexts, including studies of cellular growth, metabolism, and regeneration.

IGF-1 LR3 exerts its biological effects by binding to and activating the insulin-like growth factor-1 receptor (IGF-1R), a receptor tyrosine kinase expressed in many cell types.

Receptor Activation

The IGF-1 receptor is structurally similar to the insulin receptor. Binding of IGF-1 LR3 to the receptor's extracellular subunits induces a conformational change, leading to trans-autophosphorylation of tyrosine residues on the intracellular domains.

These phosphorylated sites act as docking points for adaptor proteins, including insulin receptor substrate (IRS) proteins and Shc. This recruitment initiates multiple downstream signaling cascades.

PI3K/Akt/mTOR Pathway

One major pathway activated is the PI3K/Akt/mTOR pathway, which is involved in protein synthesis and metabolism. Phosphorylated IRS proteins activate PI3-kinase, which leads to the activation of Akt. Akt in turn activates mTOR complex 1 (mTORC1).

Activated mTORC1 phosphorylates downstream targets like p70S6K and 4E-BP1, which are involved in regulating ribosomal biogenesis and mRNA translation, key components of protein synthesis.

Other Signaling Effects

Akt also phosphorylates and inactivates glycogen synthase kinase-3 beta (GSK3β), influencing glycogen storage. Additionally, Akt can phosphorylate and inactivate FoxO transcription factors, which are involved in the expression of genes related to cellular atrophy.

MAPK/ERK Pathway

The recruitment of Shc can lead to the activation of the MAPK/ERK pathway via Ras and MEK. The terminal kinase, ERK, translocates to the nucleus to phosphorylate transcription factors that regulate genes involved in cellular proliferation and differentiation.

Published nonclinical literature relevant to this material's molecular targets and experimental models is listed below for independent review. Findings involving other preparations or experimental systems should not be attributed to this research material.

This material is supplied solely for in vitro and other nonclinical laboratory research. It is not for human or veterinary use, consumption, administration, therapeutic use, or diagnostic use.

Laboratory Handling

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Research Limitations

Published observations involving other preparations, experimental systems, or study populations do not establish the identity, performance, or suitability of this research material for any particular experiment.