Mitogenic activities of water-soluble and -insoluble insulin conjugates.

Insulin was covalently bound to water-soluble polymers such as poly(oxyethylene) and poly(acrylic acid). The former and the latter product are water-soluble monovalent and multivalent conjugates, respectively. Insulin was also bound to a poly(acrylic acid)-grafted polystyrene film, to form a water-insoluble multivalent conjugate. The matrix polymer was prepared by graft polymerization of acrylic acid initiated by glow-discharged polystyrene film. Insulin coupled with poly(oxyethylene) reduced the mitogenic activity, but the poly(acrylic acid)-insulin conjugate stimulated cell growth more than native insulin. A concentration of immobilized insulin much lower than that of native insulin and the water-soluble insulin conjugates accelerated cell growth. The maximal mitogenic effect of the immobilized insulin was greater than that of native insulin or the water-soluble insulin conjugates. The findings suggest that the mitogenic effect of the water-insoluble, multivalent insulin conjugate lasts longer than that of the water-soluble conjugates, owing to the absence of internalization into the cell.