IGF-1 LR3 (Long R3 IGF-I) is an engineered analog of human insulin-like growth factor I with an arginine at position 3 and an N-terminal extension, designed to bind IGF-binding proteins poorly. Research consists of rat and guinea pig studies, mostly from the 1990s and 2000s.
Established: LR3 IGF-I binds IGF-binding proteins poorly and binds the type 1 IGF receptor about 3-fold less well than native IGF-I, yet was about 2.5-fold more potent than IGF-I in a rat dexamethasone model [1]. Proposed: the authors attribute its greater potency to escaping binding-protein sequestration (notably IGFBP-3) [1]; in rats, more LR3 IGF-I than IGF-I reached gut tissue, though this alone did not appear to explain its higher potency [4].
| Study | Model | Reported result | Source |
|---|---|---|---|
| IGF-I variants in dexamethasone-exposed rats [1] | Rat Male rats (150 g) given dexamethasone to induce a catabolic state; IGF-I, LR3 IGF-I or des(1-3)IGF-I for 7 days | LR3 IGF-I and des(1-3)IGF-I were about 2.5-fold more potent than IGF-I for body-weight and nitrogen measures; gut weight rose by up to 45%. | Peer-reviewed Biochemical Journal 1992 |
| Three-day infusion and small-intestine growth [2] | Rat Female rats (110 g), 3-day infusion of IGF-I or LR3 IGF-I, 5-6 per group | LR3 IGF-I, but not IGF-I, raised body weight and gut weight by about 20%; crypt length rose 13% (duodenum) and 22% (ileum). | Peer-reviewed Gut 1995 |
| Visceral organ growth in suckling rats [3] | Rat Suckling rats, 6.5-day infusion starting day 6 or 12 after birth | LR3 IGF-I was more potent than IGF-I for all growth measures; kidney and spleen weights rose by up to 85% and 76%. | Peer-reviewed American Journal of Physiology 1997 |
| Tissue delivery of LR3 IGF-I vs IGF-I [4] | Rat Preweaning (day 19) and adult rats, radiolabeled peptides, n=5-6 per group | Gut tissue held 37-50% more labeled LR3 IGF-I than IGF-I per gram; LR3 IGF-I cleared from blood faster. | Peer-reviewed Endocrinology 2003 |
| LR3 IGF-I infusion in guinea pigs [5] | Other animal Female guinea pigs (~350 g), 7-day continuous infusion | LR3 IGF-I raised relative weights of adrenals, gut, kidneys and spleen without changing overall growth; plasma IGF-I, IGF-II and binding proteins fell. | Peer-reviewed Journal of Endocrinology 1995 |
Human trials are listed for research context only; outcomes are reported in the linked publications. Animal and lab results do not establish effects in humans.
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