IGF-1 DES
Also known as: Des(1-3)IGF-1, Des IGF-1, IGF-1 Des
Evidence: Preclinical
Overview
Truncated IGF-1 missing the N-terminal Gly-Pro-Glu; about 10x as potent as IGF-1 on cultured cells, because losing Glu3 removes most IGF-binding-protein binding. Occurs naturally in colostrum, brain and uterus.
Des(1-3)IGF-1 is human IGF-1 without the N-terminal tripeptide Gly-Pro-Glu. It is not purely synthetic: it has been isolated from bovine colostrum, human brain and porcine uterus, and rat serum and tissues convert IGF-1 to it enzymatically (Ballard 1996; Yamamoto and Murphy 1995). Removing Glu3 cuts binding to the IGF-binding proteins, which makes it roughly 10 times more potent than IGF-1 at driving hypertrophy and proliferation in cultured cells; part of that advantage survives in vivo, where the anabolic effect is clearest in gut tissue (Ballard 1996). In pigs and marmosets it was the most potent of the IGFBP-poor variants for lowering plasma glucose (Tomas 1997). No clinical use was ever established and no human trial has been published; proposed clinical uses in catabolic states and inflammatory bowel disease were never evaluated.
Benefits
About 10x the potency of IGF-1 for hypertrophy and proliferation of cultured cells (in vitro); anabolic effects in rats and pigs, most marked in gut tissue; the most potent IGF-1 variant tested for glucose lowering (pig, marmoset). No human data.
Dosing reference
- Research dose
- No human data; research-community range 20 to 100 mcg per dose. Animal studies dosed by weight (42 to 270 mcg/kg bolus in marmosets, 20 to 50 mcg/kg in pigs)
- Range
- 20 to 100 mcg, 1x daily
- Reconstitution
- 1 mL bacteriostatic water
- Common vial sizes
- 0.1 mg, 1 mg
Subcutaneous or intramuscular in research use, often timed around training by community protocols. No half-life has been measured for this peptide, and no published study shows that injecting near a muscle confines the effect to it. Hypoglycemia is the documented dose-limiting effect: in pigs and marmosets des(1-3)IGF-1 was the most potent of the IGF-1 variants tested for lowering plasma glucose (Tomas 1997).
Mechanism
Des(1-3)IGF-1 is the 67-residue form of IGF-1 lacking Gly-Pro-Glu. The missing Glu3 is the residue the IGF-binding proteins need, so the peptide circulates and acts largely unsequestered; its affinity for the type-1 receptor is comparable to or slightly below that of IGF-1, which is why the potency gain is attributed to IGFBP escape rather than receptor binding (Ballard 1996; King 1992). Through IGF-1R it drives PI3K/Akt and mTOR signaling, giving about 10x the effect of IGF-1 on protein synthesis and proliferation in cultured cells. The same loss of IGFBP buffering increases insulin-receptor-mediated glucose lowering in vivo (Tomas 1997). Rat serum and tissues generate des(1-3)IGF-1 from IGF-1, so it is also an endogenous species (Yamamoto and Murphy 1995).
Evidence
Preclinical: animal or in vitro data only
- Des(1-3)IGF-1 is about 10x more potent than IGF-1 at stimulating hypertrophy and proliferation of cultured cells, from much reduced IGFBP binding caused by the absence of Glu3; it has been isolated from bovine colostrum, human brain and porcine uterus (Ballard et al., 1996)
- Rat serum and tissues convert IGF-1 to des(1-3)IGF-1 enzymatically, making it an endogenous species rather than a purely synthetic analog (Yamamoto and Murphy, 1995)
- In marmosets (42 to 270 mcg/kg) and pigs (20 and 50 mcg/kg), des(1-3)IGF-1 was the most potent of five IGF-1 variants for lowering plasma glucose (Tomas et al., 1997)
- In pigs, IGF analogs with poor IGFBP affinity produced growth and metabolic effects that differed from IGF-1 and varied with age and GH responsiveness (Walton et al., 1995)
- Human-trial status: none. The 1996 review noted clinical opportunities had not been evaluated, and none has been published since
References
- Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM, International Journal of Biochemistry & Cell Biology, 1996
- Enzymatic conversion of IGF-I to des(1-3)IGF-I in rat serum and tissues: a further potential site of growth hormone regulation of IGF-I action. Yamamoto H, Murphy LJ, Journal of Endocrinology, 1995
- IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys. Tomas FM, Walton PE, Dunshea FR, Ballard FJ, Journal of Endocrinology, 1997
- Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. King R, Wells JR, Krieg P, et al., Journal of Molecular Endocrinology, 1992
- In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness. Walton PE, Dunshea FR, Ballard FJ, Progress in Growth Factor Research, 1995
Side effects
Hypoglycemia is the documented effect: des(1-3)IGF-1 was the most potent of the IGFBP-poor IGF-1 variants at lowering plasma glucose in pigs and marmosets, with cumulative suppression several times that of IGF-1 (Tomas 1997). No human trial and no human safety data exist. IGF-1R signaling is proliferative, which is why IGF-1 analogs are studied with caution in malignancy. Injection-site swelling and pain are commonly reported (anecdotal).
Storage
- Storage
- Refrigerate 2-8°C (36-46°F)
- Lyophilized
- 2+ years at room temp, 3+ years refrigerated
- Reconstituted
- 28-30 days refrigerated
Pharmacology
- Half-life
- Not measured for this peptide; IGFBP-poor IGF-1 variants are cleared from plasma faster than IGF-1 yet suppress glucose for hours (pig, marmoset; Tomas 1997)
- Molecular weight
- 7365.4 Da
- Sequence
- TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA (67 aa; mature IGF-1 minus Gly-Pro-Glu)