Islet Pericytes Are Required for β-Cell Maturity

Diabetes. 2016 Oct;65(10):3008-14. doi: 10.2337/db16-0365. Epub 2016 Jul 7.


β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting β-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown. Here, we focus on contribution of pericytes to β-cell function. To this end, we used a transgenic mouse system that allows diphtheria toxin-based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression. Additionally, isolated islets displayed impaired glucose-stimulated insulin secretion, accompanied by a reduced expression of genes associated with β-cell function. Importantly, reduced levels of the transcription factors MafA and Pdx1 point to β-cell dedifferentiation in the absence of pericytes. Ex vivo depletion of pericytes in isolated islets resulted in a similar impairment of gene expression, implicating their direct, blood flow-independent role in maintaining β-cell maturity. To conclude, our findings suggest that pericytes are pivotal components of the islet niche, which are required for β-cell maturity and functionality. Abnormalities of islet pericytes, as implicated in type 2 diabetes, may therefore contribute to β-cell dysfunction and disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Homeostasis
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism*
  • Maf Transcription Factors, Large / genetics
  • Maf Transcription Factors, Large / metabolism
  • Male
  • Mice
  • Pancreas / cytology
  • Pancreas / metabolism
  • Pericytes / cytology*
  • Pericytes / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Homeodomain Proteins
  • MAFA protein, human
  • Maf Transcription Factors, Large
  • Nkx3-2 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein