Des(1-3)IGF-1 is a truncated analog of Insulin-like Growth Factor-I (IGF-1), a key peptide hormone structurally homologous to proinsulin and primarily produced in the liver in response to growth hormone (GH) stimulation. The ‘Des(1-3)’ designation indicates the removal of the first three N-terminal amino acids (Gly-Pro-Glu). This modification was discovered to significantly alter the peptide’s interaction with its binding proteins. Native IGF-1 circulates bound to high-affinity IGF-binding proteins (IGFBPs), which regulate its bioavailability and half-life. The Des(1-3) variant exhibits a markedly reduced affinity for IGFBP-1, allowing it to exist more freely in the bioavailable, unbound state. This characteristic has made it a valuable research tool for investigating the localized, tissue-specific actions of IGF-1 independent of the binding protein regulatory system, particularly in contexts of growth, repair, and metabolism. Its significance lies in its utility for dissecting the direct effects of IGF-1 signaling in experimental models, offering insights into anabolic processes, neuroprotection, and cellular survival pathways.
Quick Facts
| Also Known As | Des(1-3)Insulin-like Growth Factor-I, Des-N-tripeptide IGF-I, Des-IGF-1 |
|---|---|
| Sequence | GPEETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA |
| Molecular Formula | C332H527N97O101S7 |
| Molecular Weight | Approximately 7469 Da |
Research Parameters
| Half-Life | Approximately 20-30 minutes in circulation (based on rodent studies), significantly shorter than full-length IGF-1 due to reduced binding protein association. |
|---|---|
| Stability | Lyophilized powder is stable for at least 24 months when stored at -20°C, protected from light and moisture. After reconstitution in a slightly acidic buffer (e.g., acetic acid) or sterile water, it is typically stable for 7-14 days when stored at 2-8°C. Repeated freeze-thaw cycles of reconstituted peptide should be avoided. |
| Solubility | Recommended reconstitution in sterile 0.1% acetic acid or bacteriostatic water for injection. It is soluble in aqueous solutions at a slightly acidic pH. |
| Vial Size | 1 mg |
| Storage (Lyophilized) | -20°C or below, protected from light and moisture. |
| Storage (Reconstituted) | 2-8°C (refrigerated) for short-term use (typically up to 14 days). For longer storage, aliquot and store at -20°C or -80°C, avoiding repeated freeze-thaw cycles. |
| Typical Research Dose | 50-150 mcg/kg (in rodent research models) |
| Cycle Parameters | In research protocols, daily or every-other-day subcutaneous injections for a duration of 2 to 6 weeks, depending on the specific study model (e.g., muscle injury, nerve regeneration). |
| Amino Acid Count | 71 |
Mechanism of Action
Des(1-3)IGF-1 acts primarily through the IGF-1 receptor (IGF-1R), a transmembrane tyrosine kinase receptor, but with enhanced bioavailability due to its reduced sequestration by IGF-binding proteins. The primary mechanism involves the activation of the IGF-1R, which triggers a cascade of intracellular signaling events promoting cell growth, proliferation, and survival.
PI3K/Akt Pathway: Upon ligand binding and receptor autophosphorylation, insulin receptor substrate (IRS) proteins are recruited and phosphorylated. This activates phosphoinositide 3-kinase (PI3K), leading to the generation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the plasma membrane. PIP3 recruits and activates Akt (Protein Kinase B), a central node that inhibits pro-apoptotic factors like Bad and FoxO, while activating mTOR to stimulate protein synthesis and cell growth.
MAPK/ERK Pathway: Concurrently, the activated IGF-1R complex can recruit Grb2-SOS, leading to the activation of the small GTPase Ras. This initiates the Raf-MEK-ERK kinase cascade. Activated ERK translocates to the nucleus, where it phosphorylates transcription factors such as Elk-1 and c-Myc, promoting cell cycle progression and proliferation.
Reduced IGFBP-1 Binding: The key differentiating feature of Des(1-3)IGF-1 is its significantly lower affinity for IGF-binding protein-1 (IGFBP-1). This allows a greater proportion of the peptide to remain in the free, bioactive form, facilitating more potent and immediate receptor activation in local tissues compared to full-length IGF-1, which is heavily bound and regulated in circulation.
Research Applications
Musculoskeletal Research: Des(1-3)IGF-1 has been extensively studied for its potent anabolic effects on skeletal muscle and bone. In vitro and in vivo models demonstrate its ability to stimulate myoblast and satellite cell proliferation, enhance protein synthesis, and inhibit protein degradation, making it a key molecule for investigating muscle hypertrophy, regeneration after injury, and age-related sarcopenia. In bone, it promotes osteoblast activity and collagen synthesis, supporting research into fracture healing and osteoporosis.
Neurobiology and Neuroprotection: Research indicates that Des(1-3)IGF-1 can cross the blood-brain barrier more readily than full-length IGF-1 and exerts neurotrophic effects. Studies focus on its role in promoting neuronal survival, neurite outgrowth, and synaptic plasticity. It is investigated in models of neurodegenerative diseases (like Alzheimer's and Parkinson's), acute neural injury (such as stroke or trauma), and peripheral neuropathy for its potential to support neuronal repair and reduce apoptosis.
Metabolic and Glucose Homeostasis: While its primary research focus is not systemic metabolism, studies utilize Des(1-3)IGF-1 to explore the insulin-like effects of IGF-1 signaling. It has been shown to enhance glucose uptake in muscle and adipose tissue in experimental settings, providing a tool to dissect the cross-talk between IGF-1 and insulin signaling pathways and their implications for insulin sensitivity and diabetes research.
Safety & Side Effects
Data on safety and side effects are derived from animal studies. At high research doses, potential effects mirror those of excessive IGF-1 signaling and may include hypoglycemia due to its insulin-like activity, acromegaly-like symptoms (organomegaly) with chronic, systemic overexposure, and potential exacerbation of pre-existing neoplasms due to its potent mitogenic properties. Anecdotal reports from research contexts are not scientifically documented. Theoretical concerns include the risk of promoting the growth of undiagnosed tumors, cardiovascular hypertrophy, and retinopathy. Its reduced binding to IGFBPs may theoretically alter its tissue distribution and clearance compared to native IGF-1, but the full toxicological profile remains to be fully characterized.
Dosage Information
Disclaimer: The following information is derived solely from published preclinical research and is for educational purposes only. It does not constitute human dosing guidelines.
In animal research, typical doses range from 10 to 200 mcg/kg of body weight. The most common route of administration is subcutaneous injection, though intracerebroventricular, intramuscular, and local (e.g., intra-articular) injections have been used in specific studies. Dosing frequency in research protocols is often daily or every other day. Treatment duration in experimental models varies widely, from acute single-dose studies to chronic administration over several weeks, depending on the research objective (e.g., 7-14 days for muscle injury models, up to 4-6 weeks in neurodegenerative disease models).
References
Ballard, F.J., et al. 'Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I.' International Journal of Biochemistry and Cell Biology, vol. 28, no. 10, 1996, pp. 1085-1087.
Tomas, F.M., et al. 'Increased weight gain and nitrogen retention without hypertrophy in the skeletal muscle of rats treated with des(1-3) insulin-like growth factor I.' Journal of Endocrinology, vol. 134, no. 2, 1992, pp. 229-236.
Loddick, S.A., et al. 'Cerebroprotective effects of insulin-like growth factor-I (IGF-I) and des(1-3)IGF-I in a rodent model of focal ischaemia.' Journal of Cerebral Blood Flow & Metabolism, vol. 18, no. 2, 1998, pp. 176-179.
Barton, E.R., et al. 'Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice.' Journal of Cell Biology, vol. 157, no. 1, 2002, pp. 137-148.
Sara, V.R., and Hall, K. 'Insulin-like growth factors and their binding proteins.' Physiological Reviews, vol. 70, no. 3, 1990, pp. 591-614.
Carro, E., et al. 'Circulating insulin-like growth factor I mediates effects of exercise on the brain.' Journal of Neuroscience, vol. 20, no. 8, 2000, pp. 2926-2933.
Clemmons, D.R. 'Role of Insulin-Like Growth Factor I in Maintaining Normal Glucose Homeostasis.' Hormone Research, vol. 62, 2004, pp. 77-82.