OBJECTIVETo investigate the role of insulin receptor substrate 2 (IRS2) and Bax on mouse islet cell apoptosis in the presence of high glucose in vitro.

METHODSThe pancreatic islet cells were isolated from Kunming mice and divided into 6 groups (G1-G6 groups) for a 72-h culture in the media containing different concentrations of glucose (5.6, 7.8, 11.1, 16.7, 22.2, and 27.6 mmol/L, respectively). Insulin secretion by the cells was evaluated by radioimmunoassay, and the expressions of IRS2 and Bax were detected using immunocytochemistry and immunofluorescence assay, respectively. Hoechst33342 staining was employed to observe the cell apoptosis.

RESULTSExposure to 5.6-11.1 mmol/L glucose resulted in increased insulin secretion and progressive elevation of IRS2 and Bax expression, whereas the cell apoptosis underwent no obvious changes. In the presence of glucose above 16.7 mmol/L, the percentages of apoptotic islet cells increased with glucose concentration, but insulin secretion and IRS2 expression decreased; Bax expression significantly increased in the presence of high-concentration glucose.

CONCLUSIONProlonged exposure of mouse islet cells to high glucose induces apoptosis and impairs insulin secretion of the cells. Decreased IRS2 expression and increased Bax expression may play an important role in the glucotoxicity in mouse islet cells.