Fig. 7: The role of Raptor in β-cell identity maintenance and α-cell gene repression.

Raptor is required for maintaining β-cell identity as well as repressing α-cell signature. At euglycemia, loss of Raptor results in β-cell dedifferentiation (marked as UCN3^low, Glut2^low, and Aldh1a3^high) with compromised β-cell identity, metabolic uncoupling, and regression to multi-hormonal state with α-cell features. We propose Raptor/C/EBPβ/MafB-dependent and MafB-independent ways in silencing α-cell-enriched genes and glucagon expression in healthy β-cells. Raptor-deficient β-cells with compromised identity become dysfunctional and eventually cause diabetes; in turn, hyperglycemia further aggravates dedifferentiation and reprogramming process.