Proliferative effect of Apidra (insulin glulisine), a rapid-acting insulin analogue on mammary epithelial cells.

The structural modification of insulin results in the generation of insulin analogues that show altered binding affinities to the insulin receptor and/or the IGF-I receptor, and as a consequence insulin analogues may have altered mitogenic potency. We analysed the proliferative effect of the rapid-acting insulin analogue Apidra (insulin glulisine) on mammary epithelial cells. We show that Apidra and Actrapid (recombinant human insulin) have similar proliferative effects on benign MCF10A and tumorigenic MCF7 cells and on epithelial cells of mouse mammary gland. Whereas Apidra and Actrapid induced similar activation of Erk1/2, activation of Akt/PKB by Apidra was significantly weaker compared to regular insulin. As AKT/PKB, an effector of the phosphoinositide 3-kinase pathway, mediates metabolic effects of insulin, we studied induction of hexokinase-2 in MCF7 cells and hexokinase-2 and hexokinase-4 in HepG2 cells by Actrapid and Apidra. Both genes were not significantly induced by Actrapid and Apidra in these cell lines.