IGF-1 LR3: research background
What the compound is
Insulin-like growth factor-1 (IGF-1) is a protein hormone involved in various physiological processes, including growth, development, and metabolism. IGF-1 has been investigated as a therapeutic target (PMID 37261455). Long R3 IGF-1 (LR3 IGF-1 or IGF-1 LR3) is an analog of IGF-1 (PMID 37261455, PMID 39679943). It has a low affinity for IGF-binding proteins and a high affinity for the IGF-1 receptor (PMID 39679943).
How it is thought to work
LR3 IGF-1 displays bioactivity comparable to standard IGF-1 in cell proliferation assays (in cells) (PMID 37261455). IGF-1 signaling is important for maintaining plaque stability in atherosclerosis by influencing vascular smooth muscle cell (vSMC) phenotype (in cells) (PMID 21281823). IGF-1 also promotes neurogenesis, cell survival, and glial function (PMID 39610283).
What laboratory and animal studies report
In cell studies, purified IGF-1 and LR3 IGF-1 produced in a Pichia pastoris expression system showed excellent bioactivity in cell proliferation compared to standard IGF-1 (PMID 37261455). Supplementation with IGF-1 was observed to correct negative effects on vSMC function caused by macrophage-conditioned medium, such as reduced proliferation and increased apoptosis (in cells) (PMID 21281823).
In animal studies, IGF-1 LR3 administered to normal fetal sheep increased body weight but lowered insulin concentrations (in animals) (PMID 39679943). A 90-minute IGF-1 LR3 infusion in fetal sheep decreased plasma insulin concentrations and significantly lowered insulin concentrations during a hyperglycemic clamp (in animals) (PMID 37114757). However, insulin secretion in isolated fetal islets after the infusion was not different, suggesting the beta-cell's ability to recover (in animals) (PMID 37114757).
Treatment with LR3 IGF-1 in apolipoprotein E knockout mice reduced stenosis and core size, and doubled the cap/core ratio in early atherosclerosis. In advanced plaques, it increased vSMC content and significantly reduced intraplaque hemorrhage (in animals) (PMID 21281823). In fetal sheep, IGF-1-stimulated cardiac growth was accompanied by appropriate expansion and function of the coronary vasculature (in animals) (PMID 32573852). IGF-1 LR3 did not improve growth in growth-restricted fetal sheep, and it led to decreased circulating amino acids (in animals) (PMID 39679943).
In beef heifers on restricted feeding, an intravenous infusion of Long(R3)-IGF-1 tended to conserve whole-body and skeletal muscle protein (in animals) (PMID 10370861). This infusion also markedly reduced plasma concentrations of all measured amino acids and glucose, and dramatically decreased plasma IGF-2 concentrations (in animals) (PMID 10370861).
In 5XFAD male mice, intranasal LR3-IGF-1 treatment improved body composition and improved some facets of pathology in the cortex, such as a reduction in filamentous plaques and an increase in inert plaques, along with reduced low molecular weight amyloid-beta oligomers (in animals) (PMID 39610283). In vitro, LR3-IGF-1 enhanced uptake of amyloid-beta peptide by BV2 microglial cells and promoted gene pathways for actin remodeling and endocytosis (in cells) (PMID 39610283). A novel plant-based nerve conduit integrating controlled IGF-1 LR3 release significantly improved axonal regeneration in a rat sciatic nerve defect model (in animals) (PMID 41015370).
Human evidence so far
The provided abstracts do not contain specific human evidence for IGF-1 LR3 itself, although IGF-1 is mentioned as an attractive therapeutic target for clinical applications (PMID 37261455).
Open questions and limitations
In growth-restricted fetal sheep studies, IGF-1 LR3 treatment did not improve growth (in animals) (PMID 39679943). Researchers speculate that maintaining amino acid, insulin, glucose, or oxygen concentrations during IGF-1 LR3 treatment might be necessary to increase fetal growth in the presence of placental insufficiency (in animals) (PMID 39679943). While intranasal LR3-IGF-1 showed favorable effects on amyloid plaque remodeling in the cortex of male 5XFAD mice, it failed to preserve aspects of behavior or memory (in animals) (PMID 39610283), suggesting it may not be effective as a monotherapy for cognitive decline in Alzheimer's disease models.
Key terms explained
Insulin-like growth factor-1 (IGF-1): A protein hormone with roles in growth, development, and metabolism (PMID 37261455).
Long R3 IGF-1 (LR3 IGF-1): A modified version of IGF-1 with an altered binding profile, having low affinity for IGF-binding proteins and high affinity for the IGF-1 receptor (PMID 39679943).
Pichia pastoris: A yeast expression system used for recombinant protein production (PMID 37261455).
Fetal growth restriction (FGR): A complication of pregnancy where a fetus does not grow to its full potential, often linked to placental insufficiency (PMID 39679943).
Glucose-stimulated insulin secretion (GSIS): The process by which pancreatic beta-cells release insulin in response to elevated glucose levels (PMID 39679943).
Atherosclerosis: A condition characterized by the build-up of plaques in arteries (PMID 21281823).
Vascular smooth muscle cells (vSMC): Cells that make up the walls of blood vessels (PMID 21281823).
Amyloid-beta (Aβ) plaques: Abnormal protein deposits found in the brains of individuals with Alzheimer's disease (PMID 39610283).
Studies cited in this section
Summarised from the PubMed abstracts listed above. Educational reference only — not medical advice or instructions.
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