Mitogenic potency of insulin glargine

Abstract

The goal of diabetes mellitus treatment is to maintain long-term near-normoglycaemia to prevent the onset or progression of long-term complications. In order to achieve tight glycaemic control and improve the quality of life for diabetic patients, a number of novel insulin preparations, insulin analogues, have been constructed thanks to recombinant DNA technologies and advanced protein chemistry. Because structurally modified insulins may differ from human insulin not only in metabolic but also in mitogenic potencies there were concerns raised about the possibility of increased insulin analogue proliferative action or tumourigenesis. In vitro and in vivo studies on insulin analogues in comparison to endogenous insulin have been performed to closely monitor the insulin analogue action profiles. Insulin glargine was the only one presenting a significant increase in affinity to insulin-like growth factor type 1 (IGF-1) receptor. However, there was controversy regarding the safety of insulin glargine use because of its potential risk of mitogenicity but it proved to be true only for human osteosarcoma cells Saos/B10. Outcomes of the studies performed on lines other than cancer cells and on animals did not present any increased mitogenic activity nor mitogenic potency of insulin glargine in comparison to human insulin.