LAUSR

Abstract Oxidative stress is the main inducer of &bgr;‐cell damage, which underlies the pathogenesis of diabetes. Evidence suggests that glycine, a recognized antioxidant, may improve &bgr;‐cell function; however, its mechanism in protecting diabetic &bgr;‐cells against oxidative stress has not been directly investigated. Using a streptozotocin‐induced diabetic rat model and INS‐1 pancreatic &bgr;‐cells, we evaluated whether glycine can attenuate diabetic &bgr;‐cell damage induced by oxidative stress. In diabetic rats, glycine stimulated insulin secretion; enhanced plasma glutathione (GSH), catalase and superoxide dismutase levels; reduced plasma 8‐hydroxy‐2 deoxyguanosine and islet p22phox levels; and improved islet &bgr;‐cell mitochondrial degeneration and insulin granule degranulation. In INS‐1 cells, glycine reduced the intracellular reactive oxygen species (ROS) concentration and inhibited apoptosis induced by high glucose or H2O2. Glycine transporter‐1 inhibitor blocked the antioxidative effect of glycine by reducing the intracellular GSH content, and glycine receptor inhibitor reversed the glycine antioxidative effect by blocking p22phox. Collectively, our findings reveal a mechanism by which glycine protects diabetic &bgr;‐cells against damage caused by oxidative stress by increasing glycine transporter‐1‐mediated synthesis of GSH and by reducing glycine receptor‐mediated ROS production. Graphical abstract Figure. No Caption available. HighlightsEvidence suggests glycine may improve &bgr;‐cell function, but the mechanism is unclear.We used a streptozotocin‐induced diabetic rat model and INS‐1 pancreatic &bgr;‐cells.Glycine's attenuation of &bgr;‐cell damage induced by oxidative stress was evaluated.Increased transporter‐1‐mediated GSH synthesis was a primary mechanism.Reduced receptor‐mediated ROS production also contributed.