Comparison of the pharmacological profiles of glargine and its metabolites M1 and M2.

<p>(A) Conversion of glargine into M1 and M2 metabolites. (B) Effects of M1 and M2 on IR/IGF1R hybrids and on IR/IR homodimers. Receptors were prepared as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041992#pone-0041992-g001" target="_blank">figure 1</a>. BRET assays were performed in the presence of increasing concentrations of insulin, glargine, M1, M2 or IGF1. (C) Dose-dependent effect of insulin, glargine, M1, M2 or IGF1 on PIP₃ production in MCF-7 cells. BRET assays were performed in the presence of increasing concentrations of ligands. Ligand-induced BRET (BRET above basal at the plateau) was determined for each ligand concentration and was used to establish dose-response curves. Results are the means ± S.E.M. of 4 to 6 independent experiments. EC50 for insulin, IGF1, glargine and its metabolites are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041992#pone-0041992-t003" target="_blank">Table 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0041992#pone-0041992-t004" target="_blank">4</a>.