Rat hepatocyte proliferation is stimulated by insulin-like peptides in defined medium

Four purified insulin-like growth factors were compared to authentic insulin in regard to their mitogenicity on stationary phase primary cultures of adult rat hepatocytes. Under chemically defined conditions, in the presence of 0.82 mM EGF and 1.7 nM glucagon, three of these polypeptides (human somatomedin-C [SC], and human insulin-like growth factors I [IGF-I] and II [IGF-II]) stimulated DNA synthesis at physiological concentrations, as did insulin (EC 50 ∼1–3 nM). Under similar conditions, SC and IGF-I, like insulin, stimulated cell division (EC 50 ∼1–5 nM) whereas IGF-II and rat multiplication stimulating activity (MSA) were inactive. Insulin and IGF-I also were equally effective (∼0.1–0.2 nM) at lowering glucagon-induced elevations in cellular cyclic AMP levels. These results indicate that other somatomedins can exert proliferative and metabolic effects at physiological concentrations on normal hepatocytes.