Type 2 diabetes mellitus (T2DM) develops only in insulin-resistant subjects when pancreatic β-cell compensation fails (Matveyenko and Butler, 2006). Decreased insulin secretory function and reduced cell mass are traditionally viewed as major contributing factors in β-cell insufficiency. A recent study using a diabetic rodent model suggests that progressive β-cell dedifferentiation is an important underlying mechanism in β-cell failure (Talchai et al., 2012). β-cell dedifferentiation in diabetes refers to the loss by healthy β-cells of key components characteristic of the differentiated state (Dor and Glaser, 2013), including insulin (for its secretory product), Glut2 (for glucose intake), and PDX-1 (for critical insulin transcription factor). β-cell dedifferentiation may be largely responsible for not only β-cell secretory dysfunction but also impaired β-cell identity. In view of findings that bariatric surgery in a rodent T2DM model led to increased β-cell mass and improved islet morphology (Strader et al., 2009), we investigated the effects of gastric bypass surgery on dedifferentiated β-cells.