INS and obesity due to melanocortin 4 receptor deficiency: The transition from obesity and insulin resistance to T2DM is triggered by β-cell failure, impaired glucose-stimulated insulin secretion (GSIS), and loss of β-cell function that is independent of cell loss in T2DM (18, 108), which is fueled by gradual dedifferentiation of β-cells to endocrine progenitor-like cells or transdifferentiation to other cell types (109, 110).