increment nFGF1 Protects beta-Cells against High Glucose-Induced Apoptosis via the AMPK/SIRT1/PGC-1 alpha Axis

Long-term exposure to high glucose leads to beta-cell dysfunction and death. Fibroblast growth factor 1 (FGF1) has emerged as a promising diabetes treatment, but its pharmaceutical role and mechanism against glucolipotoxicity-induced beta-cell dysfunction remain uncharacterized. Wild-type FGF1 (FGF1(WT)) may exhibit in vivo mitogenicity, but deletion of N-terminal residues 1-27 gives a nonmitogenic variant, increment nFGF1, that does not promote cell proliferation and still retains the metabolic activity of FGF1(WT). To investigate the roles of increment nFGF1 on glucose regulation and potential islet beta-cell dysfunction, db/db mice were used as a model of type 2 diabetes. The results showed that insulin secretion and apoptosis of islet beta-cells were dramatically improved in increment nFGF1-treated db/db mice. To further test the effects of increment nFGF1 treatment, pancreatic beta-cell (MIN6) cells were exposed to a mixture of palmitic acid (PA) and high glucose (HG) to mimic glucolipotoxic conditions in vitro. Treatment with increment nFGF1 significantly inhibited glucolipotoxicity-induced apoptosis. Mechanistically, increment nFGF1 exerts a protective effect on beta-cells via activation of the AMPK/SIRT1/PGC-1 alpha signaling pathway. These findings demonstrate that increment nFGF1 protects pancreatic beta-cells against glucolipotoxicity-induced dysfunction and apoptosis.