Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 500, Issue 3, Pages 797-803Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.04.162
Keywords
Free fatty acid; Aloe vera; Diabetes; Beta cell; ER stress; Apoptosis
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Funding
- Ministry of Trade, Industry and Energy
- Korea Institute for Advancement of Technology through the Encouragement Program for the Economic Region Leading Industry [R0000697]
- Korea University
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Insulin resistance, a pathophysiology of type 2 diabetes, is associated with obesity. Lipotoxicity in obesity leads to the dysfunction and death of pancreatic beta-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 beta-cells in response to free fatty acids (FFAs) was determined. Hamster pancreatic beta-cell line HIT-T15 was treated with palmitate and APs to analyze cellular responses. We observed a large number of apoptotic beta-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 beta-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 beta-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 beta-cells. (C) 2018 Elsevier Inc. All rights reserved.
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