Mechanistic insights and approaches for beta cell regeneration

Nat Chem Biol. 2025 Jun;21(6):807-818. doi: 10.1038/s41589-024-01822-y. Epub 2025 Jan 29.

Abstract

Diabetes is characterized by variable loss of insulin-producing beta cells, and new regenerative approaches to increasing the functional beta cell mass of patients hold promise for reversing disease progression. In this Review, we summarize recent chemical biology breakthroughs advancing our knowledge of beta cell regeneration. We present current chemical-based tools, sensors and mechanistic insights into pathways that can be targeted to enhance beta cell regeneration in model organisms. We group the pathways according to the cellular processes they affect, that is, proliferation, conversion of other mature cell types to beta cells and beta cell differentiation from progenitor-like populations. We also suggest assays for assessing the functionality of the regenerated beta cells. Although regeneration processes differ between animal models, such as zebrafish, mice and pigs, regenerative mechanisms identified in any one animal model may be translatable to humans. Overall, chemical biology-based approaches in beta cell regeneration give hope that specific molecular pathways can be targeted to enhance beta cell regeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Diabetes Mellitus / pathology
  • Humans
  • Insulin-Secreting Cells* / cytology
  • Insulin-Secreting Cells* / drug effects
  • Insulin-Secreting Cells* / metabolism
  • Insulin-Secreting Cells* / physiology
  • Mice
  • Regeneration*