Background Pancreatic β cells are susceptible to fatty acid-induced apoptosis.The 17β-estradiol (E2) protects pancreatic β cells from apoptosis,mediated by the estrogen receptor-α (Erα).The mRNA level and promoter activity of leukemia-related protein (LRP) 16 were significantly increased by E2 in ER-α and LRP16 was a co-activator of ER-α.The aim of the study was to assess the effects of LRP16 on fatty acid-induced apoptosis in MIN6 cells.Methods Cells with over-expressing LRP16 were obtained by lipidosome transfection.Insulin content and glucose-stimulated insulin secretion (GSIS) were examined by radioimmunoassay.West blotting was applied to detect protein expression.Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)and flow cytometry.The forkhead boxO1 (FoxO1) subcellular localization was determined by immunocytochemical analysis.Results MIN6-LRP16 cells with overexpression of LRP16 were successfully established,and protein expression of LRP16 was 2.29-fold of that of control cells (MIN6-3.1,P＜0.05).Insulin content and GSIS in MIN6-LRP16 were substantially increased compared with those in control cells.When cells were stimulated with glucose,increased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and serine-threonine kinase (Akt) were observed in MIN6-LRP16.When cells were under palmitate pressure,the TUNEL-positive rate in MIN6-LRP16 was (17.0±0.5)％,while it in MIN6-3.1 was (22.0±0.4)％.In palmitate-treated cells,attenuated Akt phosphorylation was observed,but the attenuation in Akt activity was partially restored in MIN6-LRP16 cells.Meanwhile,nuclear localization of FoxO1 in MIN6-LRP16 was apparently reduced compared with that in control cells.Conclusions LRP16 regulated insulin content and GSIS in MIN6 cells by ERK1/2 and Akt activated way.Meanwhile,LRP16 overexpression protected MIN6 cells from fatty acid-induced apoptosis by partially restoring Akt phosphorylation and inhibiting FoxO1 nuclear redistribution.Therefore,LRP16 played important roles not only in insulin content and GSIS but also in the antilipotoxic effect mediated by Akt/FoxO1 signaling.