Fig. 6

(color; online only) (a) Metabolic stress (i.e., oxidative stress, proinflammatory cytokines) is a major contributor to β-cell dedifferentiation, and activation of RAS is involved in induction of metabolic stress. Angll contributes to β cell dedifferentiation via activating AT1R and the contribution is supported by the activation of NF-κb signaling. This process results in compromised β cell identity and β cell dedifferentiation (PDX1↓FOXO1↓NGN3↑), thus decreasing insulin secretion. b When NF-κb signaling is suppressed by sc-514 (IKK inhibitor), the dedifferentiation effect of Angll on β cells is alleviated (PDX1↑FOXO1↑NGN3↓), resulting in increased insulin secretion. A RAS inhibitor showed a similar effect on β cells