β-cell neogenesis: A rising star to rescue diabetes mellitus

•Progressive β-cell failure is central to the pathophysiological mechanisms of insulin-deficient diabetes mellitus.•The molecular mechanisms of β-cell failure engage multiple biological processes such as genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modifications linked to multiple signaling pathways.•The potential source of β-cell neogenesis include stimulating existing β-cell proliferation, promoting stem cell differentiation, and directing trans-differentiation of non-β-cells in the endocrine pancreas (α-cells, δ-cells, and γ-cells) and exocrine pancreas (acinar cells and ductal cells), as well as other tissues and cells such as the liver, pancreas, intestine, and endocrine progenitor-like cells.