LAUSR

HighlightsGLP‐1 analogue liraglutide increases pancreatic &bgr;‐cells autophagy under high glucose conditions;.Liraglutide inhibits pancreatic &bgr;‐cells apoptosis under high glucose conditions;.Liraglutide may protect &bgr;‐cells from high glucose by enhancing cell autophagy;.Liraglutide promotes pancreatic &bgr;‐cells autophagy through the modulation of 5′‐AMP‐activated protein kinase under high glucose conditions. ABSTRACT Glucagon‐like peptide‐1 (GLP‐1) is a potent therapeutic agent for the treatment of diabetes and has been proven to protect pancreatic &bgr;‐cells from glucotoxicity; however, its mechanisms of action are not entirely understood. Autophagy is a dynamic lysosomal degradation process that can protect organisms against metabolic stress. Studies have shown that autophagy plays a protective role in the survival of pancreatic &bgr;‐cells under high glucose conditions. In the present study, we explored the role of autophagy in GLP‐1‐induced protection of pancreatic &bgr;‐cells exposed to high glucose. We demonstrated that the GLP‐1 analogue liraglutide increased autophagy in rat INS‐1 &bgr;‐cells, and inhibition of autophagy abated the anti‐apoptosis effect of liraglutide under high glucose conditions. Our results also showed that activation of 5′‐AMP‐activated protein kinase (AMPK) reduced liraglutide‐induced autophagy enhancement and inhibited liraglutide‐induced protection of INS‐1 &bgr;‐cells from high glucose. These data suggest that GLP‐1 may protect &bgr;‐cells from glucotoxicity through promoting autophagy by the modulation of AMPK. Deeper insight into the molecular mechanisms linking autophagy and GLP‐1‐induced &bgr;‐cell protection may reveal novel therapeutic targets to preserve &bgr;‐cell mass.