Insulin as a cellular growth regulator.

Previous studies from this laboratory have shown that insulin treatment greatly stimulates liver cell growth in chronically diabetic rats. The effect is striking, being preceded by massive glycogen deposition and water imbibition as well as enchanced RNA and protein synthesis. More recently we have directly confirmed the stimulatory effects of insulin on liver RNA and glycogen synthesis in intact hepatocytes isolated from normal and diabetic rats. The hepatocytes specifically bind insulin (KD = 3.5X10(-9) M) and the bound hormone is degraded systematically, indicating the possibility of receptor-mediated uptake of the hormone. Recent studies in other laboratories of the growth factors, non-suppresible insulin-like activity (NSILA) and nerve growth factor (NGF), as well as of relaxin, have disclosed structural relationships between these peptides and pro-insulin, indicating the existence of families of closely related anabolic effectors. A new hypothesis regarding the role of the insulin-receptor complex in initiating the metabolic and mitogenic effects of the hormone is briefly discussed.