Isoferulic acid attenuates methylglyoxal-induced apoptosis in INS-1 rat pancreatic β-cell through mitochondrial survival pathways and increasing glyoxalase-1 activity

Biomed Pharmacother. 2018 May:101:777-785. doi: 10.1016/j.biopha.2018.01.017. Epub 2018 Mar 22.


Methylglyoxal (MG) is a reactive precursor to advanced glycation end-products (AGEs), which exert deleterious effects on cells and tissues. MG also causes pancreatic β-cell dysfunction and apoptosis. Isoferulic acid (IFA), a naturally occurring cinnamic acid derivative, is considered to be an antiglycating agent. However, the effect of IFA on MG-induced pancreatic β-cell dysfunction remains unknown. The objective of this study was to determine the protective effect of IFA against MG-induced mitochrondrial dysfunction and apoptosis in INS-1 pancreatic β-cells. The results showed that pretreatment of INS-1 cells with 100 μM IFA for 48 h prevented MG-induced decrease in cell viability and impairment of glucose-stimulated insulin secretion (GSIS). In addition, 100 μM IFA pretreatment also decreased MG-induced generation of reactive oxygen species (ROS) and upregulation of mitochondrial uncoupling protein 2 (Ucp2) mRNA expression. Furthermore, IFA pretreatment reduced MG-induced increase in caspase-3 activity, suggesting a reduction of apoptotic cell death. IFA (50-100 μM) itself markedly increased the activity of glyoxalase 1 (GLO1), a major enzyme for the detoxification of MG. The results showed that 100 μM IFA protected MG-induced loss of GLO1 activity in INS-1 cells. These findings suggest that IFA pretreatment attentuates MG-induced dysfunction and apoptosis in INS-1 pancreatic β-cells through mitochondrial survival pathway and increasing GLO1 activity.

Keywords: Glyoxalase-1; Isoferulic acid; Methylglyoxal; Mitochondrial uncoupling protein 2; Pancreatic β-cells.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cinnamates / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / physiology
  • Lactoylglutathione Lyase / metabolism*
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Pyruvaldehyde / toxicity*
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Cinnamates
  • Pyruvaldehyde
  • Lactoylglutathione Lyase
  • isoferulic acid