IGF-1 DES(1-3), also called DES(1-3)IGF, desamino(1-3)IGF-1, -3N:IGF-1, or DES-IGF-1, is a truncated form of insulin-like growth factor 1 (IGF-1). Compared to IGF-1, IGF-1 DES(1-3) has the first three aminos (Glycine-Proline-Glutamine) cleaved from the N-terminus; although plasma clearance rate is increased, IGF-1 DES(1-3) also exhibits a higher affinity for the IGF-1 receptor in many tissue types, and appears to bind to the receptor for an extended period. In cultured cells equal doses of IGF-1 DES(1-3) exhibit ten times greater potency at stimulating hypertrophy and proliferation compared to IGF-1. Physiologically, it appears to be generated through post-translational modification of circulating IGF-1 via protease action. This truncated form of IGF-1 has been isolated in human and bovine tissues.
IGF-1 DES (1-3) may hold promise for inflammatory disorders of the gut, and for catabolic disease states:
Des(1-3)IGF has not been tested clinically yet as success with IGF-I is considered essential before the extra expense of a more potent variant can be justified. Perhaps the more selective action of des(l-3)IGF-I on gut tissue warrants the evaluation of this growth factor as treatment for inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, which have no other effective therapies.
DES(1-3)IGF stimulates proliferation in cultured myoblasts. It binds to normal IGF-1 receptors, but has a scant 1% comparative affinity for the IGF binding proteins (IGFBP) that are nearly omnipresent; for that reason, a much lower amount of DES(1-3)IGF is as biologically active as a higher dose of IGF-1. Although the function of IGF binding proteins is not fully understood, Ballard speculates that the lack of IGF-BP affinity of IGF-1 DES(1-3) is responsible for its increased activity in gut healing and increasing nutrient uptake, due to the increased presence of IGF-BP in the gut.
While the plasma clearance rate is elevated four-fold compared to IGF-1, the metabolic effects of DES(1-3)IGF last three to five times longer. Potency varies by tissue type; in different tissues, the relative potency follows a different trend relative to normal IGF-1. Francis et al (1988) found a tenfold potency increase in rat myoblast cell lines.
IGF-1 DES(1-3) exhibits effects on collagen and bone anabolism. Despite a roughly equal receptor binding affinity in rat osteoblast cells, Canalis et al (1991) found DES (1-3) IGF-1 was as effective as IGF-1 at one-tenth the concentration:
Des-IGF I stimulated all parameters studied at 1 nM, and IGF I was effective on the labeling of DNA at 1 nM, but concentrations of 10 nM were required to observe changes in collagen and noncollagen protein synthesis and in the mitotic index. The effect of des-IGF I on collagen synthesis was independent from that on DNA synthesis, as it is known for IGF I, and both forms of IGF I were equally potent for their inhibitory effects on collagen degradation in calvarial culture.
Although DES (1-3) IGF-1 is more biologically potent in some types of tissue, the lack of IGF-BP binding may to reduce its activity in others. In a model of hypoxia-induced damage, DES (1-3) IGF-1 does not exhibit the same degree of neuroprotective effects as IGF-1 when applied two hours after blood supply to a rat brain is compromised via artery ligation:
Central administration of rh-IGF-1 after HI injury reduces neuronal loss in vivo. To clarify the mode of action of IGF-1 and the potential role of IGFBPs, the effects of IGF-1, IGF-2, des(1-3)-N-IGF-1 (des-IGF-1), an analogue of IGF-1 with low affinity for IGFBPs, and IGF-1 combined with IGF-2 were compared… Central administration of 20 micrograms IGF-1 (n = 17) reduced neuronal loss in all regions (P < 0.01). Neither 20 micrograms IGF-2 (n = 17), 2 micrograms des-IGF-1 (n = 10), nor 20 micrograms des-IGF-1 (n = 17) reduced neuronal loss. There was a trend towards a reduction in neuronal loss after 150 micrograms des-IGF-1 (n = 20).
Since DES (1-3) IGF-1 does not bind efficiently to IGF-BPs, it may exert a more local action wherever it is administered, reducing its efficacy in non-proximal injury sites. The results of Guan et al (1996) are consistent with this interpretation.
Ballard FJ Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. International Journal of Biochemistry and Cell Biology 28(10): 1085-1087 (1996)
Francis G. L., Upton F. M., Ballard F. J., McNeil K. A. and Wallace J. C. Insulin-like growth factors 1 and 2 in bovine colostrum: sequences and biological activities compared with those of a potent truncated form. Biochem. J. 251, 95-103.
Canalis E, McCarthy TL, Centrella M. Effects of desamino-(1-3)-insulin-like growth factor I on bone cell function in rat calvarial cultures. Endocrinology. 1991 Jul;129(1):534-41.
Guan J, Williams CE, Skinner SJ, Mallard EC, Gluckman PD. The effects of insulin-like growth factor (IGF)-1, IGF-2, and des-IGF-1 on neuronal loss after hypoxic-ischemic brain injury in adult rats: evidence for a role for IGF binding proteins. Endocrinology. 1996 Mar;137(3):893-8.