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.