Fig. 6: TdGSH prevents LOsG-induced β-cell dedifferentiation.

Examples of a–c islet and e–g acinar cell Nurog3 staining in sham, LOsG, and LOsG.TdGSH groups (n = 6/group); d is quantification of β-cell nuclear Nurog3 immunoreactivities (green, n = 93–100 cells/group; presented as fold changes of sham group) in islet. Examples of h–j islet and l–n acinar cell Pdx1 staining; k quantification of β-cell nuclear Pdx1 immunoreactivities (green, n = 95–99 cells/group; plotted as AU/ 10 μm²). Data are shown as mean ± SEM. ***p < 0.001 represents both LOsG versus sham or LOsG.TdGSH. ND, not detectable. White photo bar is 50 μm. O A proposed mechanism of β-cell failure. Healthy β-cells produce insulin⁺⁺ and have appropriate expressions of FoxO1⁺⁺, TXNIP⁺, and MafA⁺⁺. Long-term extra intake of carbohydrate diet could cause supraphysiological blood oscillating glycemia and ROS stress. Under this stress, β-cells would transition to two major cell subtypes depending on their traits: (1) β-cell functional failure characterized by the fall of FoxO1 expression, which in turn causes the increase of TXNIP expression and subsequently decrease MafA and insulin expression, and (2) β-cells losing their identification, which is associated with reactivation of pancreatic endocrine progenitor gene Neurog3 and Pdx1 expression, and the total loss of their capabilities to produce insulin. Subtype (1) could further transition to subtype (2) of β-cell if the stress persists. GSH can prevent all detrimental effects caused by OsG on β-cells