The species origin of the cellular microenvironment influences markers of beta cell fate and function in EndoC-βH1 cells

Exp Cell Res. 2017 Dec 15;361(2):284-291. doi: 10.1016/j.yexcr.2017.10.028. Epub 2017 Oct 31.


Interaction between islet cell subtypes and the extracellular matrix influences beta-cell function in mammals. The tissue architecture of rodent islets is very different to that of human islets; cell-to-cell communication and interaction with the extracellular matrix may vary between species. In this work, we have compared the responses of the human EndoC-βH1 cell line to non-human and human-derived growth matrices in terms of growth morphology, gene expression and glucose-stimulated insulin secretion (GSIS). EndoC-βH1 cells demonstrated a greater tendency to form cell clusters when cultured in a human microenvironment and exhibited reduced alpha cell markers at the mRNA level; mean expression difference - 0.23 and - 0.51; p = 0.009 and 0.002 for the Aristaless-related homeobox (ARX) and Glucagon (GCG) genes respectively. No differences were noted in the protein expression of mature beta cell markers such as Pdx1 and NeuroD1 were noted in EndoC-βH1 cells grown in a human microenvironment but cells were however more sensitive to glucose (4.3-fold increase in insulin secretion following glucose challenge compared with a 1.9-fold increase in cells grown in a non-human microenvironment; p = 0.0003). Our data suggests that the tissue origin of the cellular microenvironment has effects on the function of EndoC-βH1 cells in vitro, and the use of a more human-like culture microenvironment may bring benefits in terms of increased physiological relevance.

Keywords: Beta-cells; Diabetes; Microenvironment.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Communication / drug effects
  • Cell Line
  • Cellular Microenvironment / genetics*
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Gene Expression Regulation
  • Glucagon / genetics
  • Glucagon / metabolism
  • Glucose / pharmacology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Insulin / genetics
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Signal Transduction
  • Species Specificity
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • ARX protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Insulin
  • NEUROD1 protein, human
  • Trans-Activators
  • Transcription Factors
  • pancreatic and duodenal homeobox 1 protein
  • Glucagon
  • Glucose