title: Appraising the mitogenicity of insulin analogues relative to human insulin-response to: Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activity in cultured cancer cells. Diabetes Metab Res Rev 2009; 25(1): 41-9.
abstract: Interest in mitogenic and potentially carcinogenic effects of insulin and insulin analogues has been renewed by several recent publications that have examined the relationship between cancer and insulin analogues. Actions mediated through the insulin-like growth factor-I receptor in a hyperinsulinaemic state have been implicated mechanistically. Both type 2 diabetes and endogenously elevated insulin-like growth factor-I have been epidemiologically linked to malignancies. Therefore, in vitro mitogenic effects and binding affinities of the various analogues have been analysed. A recent publication by Weinstein et al. studied the in vitro mitogenic and anti-apoptotic activities of insulin analogues, and their conclusion asserts that insulins glargine, detemir, and lispro displayed proliferative and anti-apoptotic effects in a number of malignant cell lines. However, their conclusions are not supported by the data which are not complete and lack clear statistical significance. This data should be interpreted cautiously in light of all other presently available scientific evidence. Prospective, randomized clinical trials will best address any direct relationship between insulin analogues and cancer. Until those studies are designed and completed, clinicians should consider the demonstrated strong benefit of glycaemic control in balance with any alleged risk.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kazda
authors.forename: L
authors.initials: L
authors.lastname: Slieker
authors.forename: L
authors.initials: L
authors.lastname: Ilag
authors.forename: R
authors.initials: R
authors.lastname: Byrd
authors.forename: T
authors.initials: T
authors.lastname: Rees
authors.forename: M
authors.initials: M
authors.lastname: Prince
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D061268:Insulin Lispro
chemical_list: D007328:Insulin; D061268:Insulin Lispro