Somatomedin activity in plasma from burned patients with observations on plasma cortisol

Coates, Claire L.; Burwell, R. G.; Carlin, Spencer; Cason, J.S.; Littlejohn, Sheila; Selby, C.; Swannell, A J

doi:10.1016/0305-4179(81)90130-3

Cited by 18 publications

(1 citation statement)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These changes, as well as increases produced by the exogenous administration of natural or synthetic glucocorticoids such as-dexamethasone, lead to atrophy of the musculature as a consequence of decreased protein synthesis and increased protein breakdown (Goldberg, 1969;Tomas et al, 1979Tomas et al, , 1984aOdedra & Millward, 1982). The concentration of insulin-like growth factor-I (IGF-I) in blood is decreased during polytrauma or after glucocorticoid administration (Coates et al, 1981;Frayn et al, 1984;Clemmons et al, 1985;Unterman & Phillips, 1985;Mosier et al, 1987). This observation, taken together with experiments demonstrating that IGF-I stimulates protein synthesis and inhibits protein breakdown in cultured muscle cells (Ballard et al, 1986), suggest that the administration of IGF-I to glucocorticoid-treated rats may partially reverse the catabolic state, through effects on muscle protein metabolism.…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats

Tomas

Knowles

Owens

et al. 1992

Biochemical Journal

View full text Add to dashboard Cite

The administration of insulin-like growth factor-I (IGF-I) via subcutaneously implanted osmotic pumps partially reversed a catabolic state produced by the co-administration of 20 micrograms of dexamethasone/day to 150 g male rats. Marked dose-dependent effects on body weight and nitrogen retention were produced, with the highest IGF-I dose, 695 micrograms/day, giving a 6 g increase in body weight over 7 days, compared with a 19 g loss in the dexamethasone-only group and an 18 g gain in pair-fed controls. Two IGF-I analogues that bind poorly to IGF-binding proteins, the truncated form, des(1-3)IGF-I, and a variant with an N-terminal extension as well as arginine at residue 3, LR3IGF-I, were approx. 2.5-fold more potent than IGF-I. The response with LR3IGF-I was particularly striking because this peptide binds 3-fold less well than IGF-I to the type 1 IGF receptor. The increased potencies of the IGF-I variants may relate to the substantially increased plasma levels of IGF-binding proteins, particularly IGFBP-3, produced by the combined treatment of dexamethasone with IGF-I or the variants. These binding proteins would be expected to decrease the transfer of IGF-I, but not that of the variants, from blood to tissue sites of action. Measurements of muscle protein synthesis at the end of the treatment period and muscle protein breakdown by 3-methylhistidine (3MH) excretion throughout the experiment indicated coordinate anabolic effects of the IGF peptides on both processes. Thus 3MH excretion was decreased at the highest IGF-I dose from 83.5 +/- 4.2 (S.E.M.) mumol/kg per 7 days to 65.1 +/- 2.2, compared with 54.9 +/- 1.2 in the pair-fed controls. Part of this response in 3MH excretion may have reflected a decrease in gut protein breakdown, because IGF-I and especially the IGF analogues increased the gut weight by up to 45%. Notwithstanding the effects on protein synthesis and breakdown, the fractional carcass weights remained low in the IGF-treated groups, although the increase in total carcass weight reflected nitrogen rather than fat gain. The dexamethasone-induced changes in liver, spleen and heart weight were restored towards normal by the IGF treatment. The experiment demonstrates the potential of IGF-I treatment of catabolic states and especially the value of modified forms of growth factors that bind weakly to IGF-binding proteins.

show abstract

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats

Tomas

Knowles

Owens

et al. 1992

Biochemical Journal

View full text Add to dashboard Cite

show abstract

Growth Factors in Nutritional Support

Hatton,

Luer,

Rapp

1993

Pharmacotherapy

View full text Add to dashboard Cite

Protein catabolism occurs in the severely stressed patient despite adequate protein supplementation. Supplementation of endogenous growth factors is one mechanism being evaluated to promote anabolism and improve nitrogen retention. Recombinant technology has provided a means to reproduce these endogenous growth factors. Both recombinant human growth hormone (rGH) and recombinant human insulin‐like growth factor‐1 (rhIGf‐1) are undergoing clinical trials to establish their roles in nutritional support.

show abstract