Stimulation of cardiac protein synthesis by insulin-like growth factors.
The effects of the insulin-like growth factors (IGF)-1 and -2 on the rates of protein synthesis in freshly isolated cardiac myocytes from adult rats were compared with those of insulin. At concentrations of 50-100 nM, each agent stimulated protein synthesis by about 70%. There was no additional stimulation upon combination of insulin with IGF-1 or IGF-2 at these high concentrations. When compared over a range of concentrations, the relative response to each agent was insulin greater than IGF-1 greater than or equal to IGF-2. Concentrations of 1 nM-IGF-1, 1 nM-IGF-2 or 0.2 nM-insulin enhanced the rates of protein synthesis by 36%, 30% or 34% respectively. A combination of 0.2 nM-insulin and 1 nM-IGF-1 or 1 nM-IGF-2 increased the stimulation of protein synthesis to 46%. In contrast, the effects of 1 nM-IGF-1 and 1 nM-IGF-2 were not additive. The possible mechanistic basis for this difference is discussed. At a concentration of 50 nM, epidermal growth factor (EGF), fibroblast growth factor and platelet-derived growth factor were each without effect on protein synthesis. In anterogradely perfused rat heart preparations, 2 nM-IGF-1 or 2.4 nM-IGF-2 increased protein synthesis and lactate production, but 9.2 nM-EGF did not. From a consideration of the plasma free concentrations of IGF-1 and IGF-2, we suggest that these factors may contribute to the maintenance of rate of cardiac protein synthesis in vivo.
Fuller
S J
SJ
Department of Cardiac Medicine, National Heart and Lung Institute (University of London), U.K.
Mynett
J R
JR
Sugden
P H
PH
D000818:Animals; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D002250:Carbon Radioisotopes; D007328:Insulin; D011994:Recombinant Proteins; D010649:Phenylalanine; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II