Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig

Preclinical integrated pharmacology study of Long R3 IGF-I (LR3-IGF-I) in adult guinea pigs, conducted by the same Australian CSIRO group responsible for the analog's design. The focus was to characterize systemic effects of prolonged infusion of the low-IGFBP-affinity analog, comparing them to native IGF-1 and IGF-2.

The design used continuous subcutaneous infusion for 7 days via osmotic pump in female guinea pigs. Groups received recombinant IGF-1, recombinant IGF-2, or LR3-IGF-I, always at 120 µg/day. Outcomes included body weight, individual organ weights (liver, kidney, spleen, adrenals, gonads, intestine), plasma levels of IGF-1, IGF-2 and IGFBPs, and hematologic markers.

LR3-IGF-I produced significant organ-specific growth — particularly in adrenals, intestine, kidneys and spleen — without proportional change in total body weight. This pattern is consistent with the theory that lower IGFBP binding increases tissue availability of the analog, especially in densely vascularized organs. Paradoxically, infusion reduced plasma concentrations of endogenous IGF-1, IGF-2 and IGFBPs — probably by negative feedback on the hepatic GH-IGF axis and suppression of IGFBP-3 production.

This work is a classic reference for understanding that LR3 is not simply a more potent IGF-1 — it has different tissue distribution and pharmacodynamics from the native hormone. The finding of disproportionate visceral growth (including gut and adrenals) is especially relevant to the debate on safety of prolonged use: visceral hypertrophy may be an overlooked concern in bodybuilding protocols. The study remains a fundamental reference in the literature on IGF-1 analogs.