Human islets contain four distinct subtypes of β cells

Nat Commun. 2016 Jul 11;7:11756. doi: 10.1038/ncomms11756.

Abstract

Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human β cells, which we refer to as β1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the β cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined β cell heterogeneity is functionally and likely medically relevant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Flow Cytometry
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans
  • Male
  • Middle Aged
  • Sialyltransferases / metabolism*
  • Tetraspanin 29 / metabolism*
  • Young Adult

Substances

  • CD9 protein, human
  • Glycated Hemoglobin A
  • Tetraspanin 29
  • hemoglobin A1c protein, human
  • Sialyltransferases
  • alpha-N-acetylneuraminate alpha-2,8-sialyltransferase