IGF-DES dosage protocol

What the compound is

Des(1-3)IGF-1, also referred to as IGF-DES, is an analog of insulin-like growth factor-1 (IGF-1) (PMID 12745670). It is a truncated form of IGF-1, missing the first three amino acids (PMID 2973786, PMID 2559737). This structural difference leads to a key characteristic: IGF-DES has a low affinity for insulin-like growth factor-binding proteins (IGFBPs), particularly the small IGFBPs (PMID 2539101, PMID 2973786). This low binding affinity is thought to contribute to its increased biological potency compared to IGF-1 and IGF-2 in some contexts (PMID 2539101, PMID 2559737).

How it is thought to work

IGFs generally stimulate protein synthesis and inhibit protein degradation in cultured cells (PMID 2559737). IGF-DES's enhanced biological activity is hypothesized to result from higher concentrations of the free peptide, as it binds poorly to IGFBPs released from most cell types (PMID 2539101, PMID 2559737). However, it retains a long biological half-life because it can still attach to blood IGF-binding proteins (PMID 2559737). The binding of IGF-1 and IGF-2 to IGFBPs can reduce their accessibility to the type 1 IGF receptor, whereas IGF-DES's activity is not inhibited by these binding proteins (PMID 2539101).

What laboratory and animal studies report

In cell studies, a binding protein purified from bovine kidney cells or human amniotic fluid inhibited the biological activities of IGF-1 and IGF-2, but did not influence the activities of IGF-DES (PMID 2539101). Pre-clinical trials using cells showed that vitamin D can decrease the proliferation of benign prostatic hyperplasia (BPH) cells and prostate cells when induced by growth-promoting molecules such as IGF-DES (PMID 23930605).

Animal studies in diabetic rats found that systemic IGF-DES treatment normalized abnormal accumulations of type 1 IGF receptor and phospho-Akt (Thr 308) immunoreactivity in the retinas, which are early biochemical abnormalities linked to diabetic retinopathy progression. This effect occurred despite ongoing hyperglycemia and a failure of weight gain in the treated rats (PMID 12745670). In an olfactory bulb organ culture system (an in vitro injury model), IGF-DES was found to be ineffective in enhancing neuronal survival, contrasting with IGF-1, which supports a role for local IGFBPs in transport or receptor targeting (PMID 9554468).

In rats, IGF-DES had a shorter half-life in blood and a slower influx rate into the brain compared to IGF-1, and its pharmacokinetics were not altered by the addition of nonradiolabeled peptide (PMID 11025411). Studies in aging male Brown Norway rats showed a decline in cortical protein synthesis with age. While IGF-1, IGF-DES, or insulin stimulated protein synthesis in cortical slices from young animals, this response was blunted in old animals (PMID 7609879).

Open questions and limitations

The preliminary results from diabetic rats suggested that vascular endothelial growth factor (VEGF) levels might also be reduced with IGF-DES treatment, but this requires further confirmation (PMID 12745670). The contrasting efficacy of IGF-DES versus IGF-1 in the olfactory bulb organ culture model highlights the complex interplay of IGFBPs and their role in targeting IGFs to receptors (PMID 9554468). Further research is needed to fully understand the biological significance of IGFs and to potentially develop mutant IGF-1 molecules for therapeutic applications (PMID 2559737).

Key terms explained

Insulin-like Growth Factor-1 (IGF-1): A protein that plays a role in growth and development (PMID 9554468).

Insulin-like Growth Factor-Binding Proteins (IGFBPs): Proteins that bind to IGFs, influencing their availability and activity (PMID 2539101, PMID 9554468).

Type 1 IGF receptor: A receptor on cells that IGFs bind to in order to exert their effects (PMID 2539101).

Phospho-Akt (Thr 308) immunoreactivity: A marker indicating the activation of the Akt signaling pathway, which is involved in cell survival and growth (PMID 12745670).