IGF-1 LR3, also called insulin-like growth factor 1 (long arginine), is a modified synthetic version of endogenous insulin-like growth factor 1 (IGF-1). IGF-1 is a growth factor that is produced by the liver (endocrine) and local cells (autocrine/paracrine) throughout the lifespan; IGF-1 plays a key role in development and exerts an anti-catabolic effect in skeletal muscle tissue. IGF-1 (Increlex) is approved for treatment of various types of GH/IGF-1 deficiency. Prospective areas for development of IGF-1 or analogs include neuroprotection, post-injury or post-surgical healing, and as a treatment for muscle wasting disorders.
Physiological IGF-1 plays a key role in normal and abnormal growth; it is capable of inducing cell proliferation as well as inhibiting apoptosis. Creaney and Hamilton (2008) discuss the origin, roles, and clinical/diagnostic significance of physiological IGF-1:
IGF-1 is a 7.5 kDa polypeptide that is structurally similar to insulin.50 It induces proliferation, differentiation and hypertrophy of multiple cell lines, in particular skeletal muscle, and has an additional role of facilitating glucose entry into skeletal muscle cells... IGF-1 is secreted as the result of a hypothalamic-pituitary liver axis. The hypothalamus secretes growth hormone-releasing hormone (GHRH), which stimulates the pituitary to release growth hormone, which in turn stimulates the liver to release IGF-1. Like most endocrine systems, the system is controlled by negative feedback, thus in normal individuals, exogenous administration of IGF-1 will lead to suppression of the axis. Whereas growth hormone secretion is pulsatile, with greatly varying levels in a 24-hour period, serum IGF-1 levels are relatively stable within a 24-hour period; hence, measurement of the serum IGF-1 level is now the favoured test for acromegaly or growth hormone deficiency
Higher IGF-1 levels correlate with a variety of apparent benefits, at least in some groups: neuroprotective, pro-intelligence, pro-synaptogenic, pro-myelinatory, and pro-lean-body-mass effects have been documented in humans (including children) and animals.
Compared to endogenous or recombinant IGF-1, the long arginine form (IGF-1 LR3) is more potent and longer-lasting, allowing it to circulate for twenty-four hours or more and reach more targets.
IGF-1, administered from an exogenous source, protects muscle cells from oxidative damage; Yang et al (2010) suggest this is promising in offering a treatment for muscle wasting states or pathologies such as Duchenne muscular dystrophy and sarcopenia (aging-related loss of muscle mass).
IGF-1 is also neurotrophic in some circumstances; according to Rabinovsky (2003) "nerve sprouting within skeletal muscles is an essential restorative process in response to an injury or a pathological condition. IGF-1 increases intramuscular nerve sprouting 10-fold when administered subcutaneously to normal adult rats" and also that "IGF-1 is also a potent myogenic factor, promoting myoblast proliferation, myogenic differentiation, and myotube hypertrophy”. The efficacy of IGF-1 for neurotrophic or neuroprotective effects is predicted by its physiological role: "when the sciatic nerve is injured,increased local expression of IGF-1 in muscle hastens motor nerve and muscle repair".
Creaney L and Hamilton B. Growth factor delivery methods in the management of sports injuries: the state of play. Br J Sports Med. 2008 May;42(5):314-20.
Dunshea FR, Chung CS, Owens PC, Ballard JF, Walton PE. Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs. Br J Nutr. 2002 Jun;87(6):587-93.
Gunnell D, Miller LL, Rogers I, Holly JM; ALSPAC Study Team. (2005). Association of insulin-like growth factor I and insulin-like growth factor-binding protein-3 with intelligence quotient among 8- to 9-year-old children in the Avon Longitudinal Study of Parents and Children. Pediatrics. Nov;116(5):e681-6.
Yang SY, Hoy M, Fuller B, Sales KM, Seifalian AM, Winslet MC. Pretreatment with insulin-like growth factor I protects skeletal muscle cells against oxidative damage via PI3K/Akt and ERK1/2 MAPK pathways. Lab Invest. 2010 Mar;90(3):391-401.
Rabinovsky ED, Gelir E, Gelir S, Lui H, Kattash M, DeMayo FJ, Shenaq SM, Schwartz RJ. Targeted expression of IGF-1 transgene to skeletal muscle accelerates muscle and motor neuron regeneration. Jan 2003. The FASEB Journal vol. 17 no. 1 53-55.