Prolonged hyperglycemia leads to oxidative stress, endoplasmic reticulum (ER) stress, hypoxic stress and cytokine induction leading to β-cell compensation, stress and later failure and de-differentiation.

Βeta-cell identity is fragile, but islet identity is stable: islet cells share chromatin structure and methylome. Other than hormone genes, they represent flexibility and plasticity states rather than stable subtypes.

FoxO1 plays an important role in the de-differentiation and re-differentiation of β cells. Reprogramming of other cell types to β cells is a possibility and can be a potential treatment option for diabetes in the future.

Glucagon-like peptide 1 (GLP-1), sodium-glucose Cotransporter-2 (SGLT2) inhibitors, thiazolidinediones, metformin and intensive insulin therapy offer β-cell protection and preservation.