The protective effect of APPL1 on high glucose or cytokines-induced pancreatic β-cell apoptosis and dysfunction

Abstract

Objective To determine the role of APPL1,an adaptor protein,played in pancreatic β-cell.Methods APPL1 was overexpressed in INS-1 cells with adenovirus encoding APPL1.Western blot was conducted to measure protein cxprcssion.Propidium iodide/Hoechst staining was used to determine the cell apoptosis.Insulin secretion was measured by ELISA.Results Exposure of INS-1 cells to 20 mmol/L glucose or 30U/ml interleukin-1 β plus 20 ng/ml TNF-α 48 h induced β-cell apoptosis (P＜0.01) and impaired 2 h glucosestimulated insulin secretion (P＜ 0.01).Overexpression of APPL1 in INS-1 decreased cell apoptosis by 34.16％-42.79％ (P＜0.01) and increased glucose-induced insulin secretion by 1.39-2.20 folds compared with control groups (P＜0.05).Conclusion APPL1 decreases β-cell apoptosis and increases glucose-stimulated insulin secretion,and thus protects β-cell against high glucose or cytokines-induced dysfunction. Key words: APPL1 ; Cell apoptosis; Insulin secretion