HDLs protect the MIN6 insulinoma cell line against tunicamycin-induced apoptosis without inhibiting ER stress and without restoring ER functionality

Mol Cell Endocrinol. 2013 Dec 5;381(1-2):291-301. doi: 10.1016/j.mce.2013.08.016. Epub 2013 Aug 28.


HDLs protect pancreatic beta cells against apoptosis induced by several endoplasmic reticulum (ER) stressors, including thapsigargin, cyclopiazonic acid, palmitate and insulin over-expression. This protection is mediated by the capacity of HDLs to maintain proper ER morphology and ER functions such as protein folding and trafficking. Here, we identified a distinct mode of protection exerted by HDLs in beta cells challenged with tunicamycin (TM), a protein glycosylation inhibitor inducing ER stress. HDLs were found to inhibit apoptosis induced by TM in the MIN6 insulinoma cell line and this correlated with the maintenance of a normal ER morphology. Surprisingly however, this protective response was neither associated with a significant ER stress reduction, nor with restoration of protein folding and trafficking in the ER. These data indicate that HDLs can use at least two mechanisms to protect beta cells against ER stressors. One that relies on the maintenance of ER function and one that operates independently of ER function modulation. The capacity of HDLs to activate several anti-apoptotic pathways in beta cells may explain their ability to efficiently protect these cells against a variety of insults.

Keywords: Apoptosis; Endoplasmic reticulum; HDL; Pancreatic beta cell; Tunicamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cytoprotection
  • DNA-Binding Proteins / metabolism
  • Endoplasmic Reticulum / physiology*
  • Endoplasmic Reticulum / ultrastructure
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • HEK293 Cells
  • Heat-Shock Proteins / metabolism
  • Humans
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipoproteins, HDL / physiology*
  • MAP Kinase Signaling System
  • Mice
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / metabolism
  • Regulatory Factor X Transcription Factors
  • Thapsigargin / pharmacology
  • Transcription Factor CHOP / metabolism
  • Transcription Factors / metabolism
  • Tunicamycin / pharmacology*


  • DNA-Binding Proteins
  • Ddit3 protein, mouse
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins
  • Lipoproteins, HDL
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • Tunicamycin
  • Transcription Factor CHOP
  • Thapsigargin
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases