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Protopanaxadiol ameliorates palmitate-induced lipotoxicity and pancreatic β-cell dysfunction in INS-1 cells

  • Dahae Lee (College of Korean Medicine, Gachon University) ;
  • Sungyoul Choi (College of Korean Medicine, Gachon University) ;
  • Ki Sung Kang (College of Korean Medicine, Gachon University)
  • Received : 2022.04.30
  • Accepted : 2023.02.12
  • Published : 2023.07.01

Abstract

Background: Free fatty acid-induced lipotoxicity is considered to play an important role in pancreatic β-cell dysfunction. The effect of ginsenosides on palmitic acid-induced pancreatic beta-cells cell death and failure of glucose-stimulated secretion of insulin (GSIS) was evaluated in this study. Methods: Enzyme-linked immunosorbent assay kit for a rat insulin was used to quantify glucose-stimulated insulin secretion. Protein expression was examined by western blotting analysis. Nuclear condensation was measured by staining with Hoechst 33342 stain. Apoptotic cell death was assessed by staining with Annexin V. Oil Red O staining was used to measure lipid accumulation. Results: We screened ginsenosides to prevent palmitic acid-induced cell death and impairment of GSIS in INS-1 pancreatic β-cells and identified protopanaxadiol (PPD) as a potential therapeutic agent. The protection effect of PPD was likely due to a reduction in apoptosis and lipid accumulation. PPD attenuated the palmitic acid-induced increase in the levels of B-cell lymphoma-2-associated X/B-cell lymphoma 2, poly (ADP-ribose) polymerase and cleaved caspase-3. Moreover, PPD prevented palmitic acid-induced impairment of insulin secretion, which was accompanied by an increase in the activation of phosphatidylinositol 3-kinase, peroxisome proliferator-activated receptor γ, insulin receptor substrate-2, serine-threonine kinase, and pancreatic and duodenal homeobox-1. Conclusion: Our results suggest that the protective effect of PPD on lipotoxicity and lipid accumulation induced by palmitic acid in pancreatic β-cells.

Keywords

Acknowledgement

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1A6A3A01100467, 2020M3A9E410438021). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1F1A1073551).

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