IGF-1 LR3

Effects measured: LR3 IGF-I alone DECREASED average daily weight gain and feed intake rather than increasing them. Mean plasma growth hormone fell about 23% and the area under GH peaks fell about 60%. Endogenous plasma IGF-I and IGFBP-3 were also suppressed. Combining LR3 IGF-I with porcine GH did not rescue growth; insulin, IGFBP-3 and IGF-I stayed suppressed. The authors concluded the IGF peptide suppressed GH secretion, which secondarily lowered the IGF axis and contributed to growth inhibition in this model.

Side effects: No adverse events reported in this study (the suppressed growth, GH, IGF-I and IGFBP-3 were the measured pharmacological outcomes, not flagged as toxicity)

Sources: Dunaiski, Dunshea, Walton, Goddard. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs. J Endocrinol. 1997.

Effects measured: At an equal 2.5 mg/kg/day dose, LR3 IGF-I but NOT native IGF-I increased body weight and increased the wet weight of both small and large intestine by about 20% versus controls. Duodenal crypt length rose about 13% and ileal crypt length about 22%, with more cells per crypt. Tritiated-thymidine labelling index (cell proliferation marker) rose up to about 14% in duodenum and ileum. The colon labelling index stayed low with non-significant change. This illustrates that LR3 is more potent than native IGF-I in vivo because it escapes IGF binding proteins.

Side effects: No adverse events reported in this study

Sources: Steeb CB, Trahair JF, Read LC. Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats. Gut. 1995.

Effects measured: LR3 IGF-I significantly increased the fractional (per-body-weight) weights of adrenals, gut, kidneys and spleen, showing selective organ growth. However whole-body weight gain and feed intake were NOT significantly changed. At the same time circulating plasma IGF-I, IGF-II and IGF binding protein concentrations were reduced. So the analogue redistributed growth to specific organs without driving net body-weight gain in this short study.

Side effects: No adverse events reported in this study

Sources: Conlon MA, Tomas FM, Owens PC, Wallace JC, Howarth GS, Ballard FJ. 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. J Endocrinol. 1995.

Effects measured: Long[R3]IGF-I increased fibroblast cell number and was more potent than native IGF-I: half-maximal proliferative effect at about 0.6 nM for Long[R3]IGF-I versus about 1.5 nM for IGF-I. The greater potency is attributed to LR3 escaping the inhibitory IGF binding proteins (IGFBP-3, IGFBP-4) that the cells secrete. This is a mechanistic potency comparison, not a tissue-growth outcome.

Side effects: No adverse events reported in this study (in vitro)

Sources: Price WA. Regulation of insulin-like growth factor (IGF)-binding protein expression by growth factors and cytokines alters IGF-mediated proliferation of postnatal lung fibroblasts. Exp Lung Res. 2004.

Effects measured: The reduced-IGFBP-affinity analogues long R3-IGF-I and des(1-3)IGF-I produced GREATER effects on DNA synthesis than native IGF-I in purified rat theca-interstitial cells. The abstract reports a qualitative comparison (greater proliferative effect) but does not give a numerical fold-change or thymidine-incorporation value. The authors note this may help explain thecal and stromal hyperplasia in hyperinsulinaemic conditions such as polycystic ovary syndrome.

Side effects: No adverse events reported in this study (in vitro)

Sources: Duleba AJ, Spaczynski RZ, Olive DL, Behrman HR. Effects of insulin and insulin-like growth factors on proliferation of rat ovarian theca-interstitial cells. Biol Reprod. 1997.