Metformin‐induced autophagy and irisin improves INS‐1 cell function and survival in high‐glucose environment via AMPK/SIRT1/PGC‐1α signal pathway

In order to explore the protective function of metformin on pancreatic β cells to alleviate insulin resistance and underlying mechanisms, INS‐1 cells were cultured into normal control (N), high glucose (H), high glucose and metformin (H + Met), high glucose and chloroquine (H + CQ), and high glucose and Ex527 (H + Ex527) groups, respectively. Upon 24‐hr cultivation, the proliferation and glucose‐stimulated insulin secretion (GSIS) of INS‐1 cells were determined, and the expression of irisin and other proteins associated with AMPK/SIRT1/PGC‐1α signal pathway, autophagy, and apoptosis was evaluated. Compared with the N group, the cells from the H group revealed lower proliferation, GSIS, and expression of irisin and proteins associated with AMPK/SIRT1/PGC‐1α signal pathway and autophagy, but higher expression of proteins associated with apoptosis; in contrast, metformin could significantly rescue lower cell proliferation, GSIS, and expression of proteins associated with AMPK/SIRT1/PGC‐1α signal pathway and autophagy, as well as irisin, and suppress apoptosis in high‐glucose environment. Meanwhile, autophagy inhibitor CQ and SIRT1 inhibitor Ex527 can block above functions of metformin. Therefore, metformin can promote INS‐1 cell proliferation, enhance GSIS, and suppress apoptosis by activating AMPK/SIRT1/PGC‐1α signal pathway, up‐regulating irisin expression, and inducing autophagy in INS‐1 cells in high‐glucose environment.