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 > IGF-1 greater-than-or-equal-to IGF-2. Concentration 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.