title: Proliferative effect of Apidra (insulin glulisine), a rapid-acting insulin analogue on mammary epithelial cells.
abstract: 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.
authors.affiliation: Hormones and Signal Transduction, German Cancer Research Centre, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Ashish
authors.initials: A
authors.lastname: Shukla
authors.forename: Harald
authors.initials: H
authors.lastname: Enzmann
authors.forename: Doris
authors.initials: D
authors.lastname: Mayer
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects; D042361:Mammary Glands, Human / Q000166:cytology* / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007328:Insulin; D011994:Recombinant Proteins; D017526:Receptor, IGF Type 1