ER stress attenuation by Aloe-derived polysaccharides in the protection of pancreatic β-cells from free fatty acid-induced lipotoxicity

Kisoo Kim, Min Hwa Chung, Soyoung Park, Jimin Cha, Jin Hong Baek, Shin Young Lee, Sang-Yun Choi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Insulin resistance, a pathophysiology of type 2 diabetes, is associated with obesity. Lipotoxicity in obesity leads to the dysfunction and death of pancreatic β-cells and inadequate insulin production, thereby aggravating type 2 diabetes. The present study was conducted to determine the effect of Aloe vera polysaccharides (APs) as an anti-hyperglycemic agent and their mechanisms of action. Gel polysaccharides from Aloe extracts were separated using ultrafiltration devices with molecular weight-cutoff membranes, and the protective effect of APs on pancreatic β-cells in response to free fatty acids (FFAs) was determined. Hamster pancreatic β-cell line HIT-T15 was treated with palmitate and APs to analyze cellular responses. We observed a large number of apoptotic β-cell death after treatment with high levels of palmitate, but this was efficiently prevented by the addition of APs in a dose-dependent manner. It was found that the anti-apoptotic properties of APs were largely due to the relief of endoplasmic reticulum (ER) stress signaling. APs were effective in interfering with the FFA-induced activation of the PERK and IRE1 pathways as well as ROS generation, thereby protecting pancreatic β-cells from lipotoxicity. Although variation in the chain length of APs can influence the activity of FFA-mediated ER stress signaling in different ways, polysaccharide mixtures with molecular weights higher than 50 kDa showed greater antiapoptotic and antioxidant activity in β-cells. After oral administration of APs, markedly lowering fasting blood glucose levels were observed in db/db mice, providing evidence of the potential of APs as an alternative insulin sensitizer. Therefore, it was concluded that APs have a protective effect against type 2 diabetes by modulating obesity-induced ER stress in pancreatic β-cells.

Original languageEnglish
Pages (from-to)797-803
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume500
Issue number3
DOIs
Publication statusPublished - 2018 Jun 7

Keywords

  • Aloe vera
  • Apoptosis
  • Beta cell
  • Diabetes
  • ER stress
  • Free fatty acid

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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