Nutrient overload increases oxidative stress (e.g., ROS) in beta cells. Consequently, ROS causes beta-cell dysfunction and death and, in turn, type 2 diabetes (T2D). Of note, Pdia4 was first identified as a central player that controls ROS production in beta cells. Conversely, a Pdia4 inhibitor, PS-001, can preserve beta cell mass and function and, subsequently, reverse diabetes. This preservation involves novel mechanism - inhibition of Pdia4-mediated ROS production pathways.
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