A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell-related glycolipids, sulfatide and β-galactosylceramide

Diabetes Metab Res Rev. 2010 Nov;26(8):656-67. doi: 10.1002/dmrr.1134. Epub 2010 Oct 14.


Background: T1DM is a T-cell-mediated autoimmune disease targeting insulin-producing beta-cells. Multiple factors may contribute to the development of T1DM. Among these, the metabolic state of beta-cells and pro-inflammatory cytokines, produced by infiltrating immune cells, have been implicated in the precipitation of T1DM.

Methods and results: In this study, confocal immunofluorescence microscopy of human pancreata revealed a distinct subset of beta-cells expressing the innate LPS co-receptor CD14. Human islets expressed fully functional CD14 as LPS stimulation led to a dose-dependent secretion of tumour necrosis factor (TNFα), interleukin (IL)-1β and IL-8, which were substantially inhibited by a blocking anti-CD14 mAb. In addition, LPS stimulation impaired the glucose-mediated insulin secretion in rat islets. β-GalCer and sulfatide, glycolipids that are related to insulin processing and secretion, are possibly interacting with the CD14 receptor complex. β-GalCer had an LPS-like, serum- and CD14-dependent effect on the induction of pro-inflammatory cytokines in a human monocyte cell line. In contrast, the LPS-mediated cytokine production was inhibited by sulfatide. Human islets also responded to β-GalCer (10 µg/mL) by secreting TNFα, IL-1β and IL-8, whereas sulfatide partly inhibited the effect of LPS.

Conclusions: A subset of human beta-cells expresses functional CD14 receptor and thus is able to recognize both exogenous bacterial (LPS) as well as endogenous ligands (e.g. glycolipids of beta-cell origin). The CD14 expression on a subset of human beta-cells may play a role in the innate surveillance of the endocrine environment but may also contribute to innate immune mechanisms in the early stages of beta-cell aggression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cells, Cultured
  • Female
  • Galactosylceramides / metabolism
  • Glycolipids / metabolism
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Interleukin-8
  • Lipopolysaccharide Receptors / biosynthesis*
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • Rats
  • Signal Transduction
  • Sulfoglycosphingolipids / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Galactosylceramides
  • Glycolipids
  • Interleukin-8
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Sulfoglycosphingolipids
  • Tumor Necrosis Factor-alpha