Pancreatic β-cell heterogeneity in health and diabetes: Classes, sources, and subtypes

Mario A. Miranda, Juan F. Macias-Velasco, Heather A. Lawson

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations


Pancreatic β-cells perform glucose-stimulated insulin secretion, a process at the center of type 2 diabetes etiology. Efforts to understand how β-cells behave in healthy and stressful conditions have revealed a wide degree of morphological, functional, and transcriptional heterogeneity. Sources of heterogeneity include β-cell topography, developmental origin, maturation state, and stress response. Advances in sequencing and imaging technologies have led to the identification of β-cell subtypes, which play distinct roles in the islet niche. This review examines β-cell heterogeneity from morphological, functional, and transcriptional perspectives, and considers the relevance of topography, maturation, development, and stress response. It also discusses how these factors have been used to identify β-cell subtypes, and how heterogeneity is impacted by diabetes. We examine open questions in the field and discuss recent technological innovations that could advance understanding of β-cell heterogeneity in health and disease.

Original languageEnglish
Pages (from-to)E716-E731
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number4
StatePublished - Apr 2021


  • Diabetes
  • Insulin secretion
  • Insulin secretion
  • β-cell heterogeneity
  • β-cell heterogeneity
  • β-cell subtype
  • β-cell subtype


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