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Lupin γ-conglutin protects against cell death induced by oxidative stress and lipotoxicity, but transiently inhibits in vitro insulin secretion by increasing KATP channel currents

Lupin γ-conglutin beneficially modulates glycemia, but whether it protects against oxidative and lipotoxic damage remains unknown. Here, we studied the effects of γ-conglutin on cell death provoked by hydrogen peroxide and palmitate in HepG2 hepatocytes and insulin-producing MIN6 cells, and if a mod...

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Published in:International journal of biological macromolecules 2021-09, Vol.187, p.76-90
Main Authors: Guzmán, Tereso J., Düfer, Martina, Wiedemann, Mats, Olguín-Alor, Roxana, Soldevila, Gloria, Gurrola-Díaz, Carmen M.
Format: Article
Language:English
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Summary:Lupin γ-conglutin beneficially modulates glycemia, but whether it protects against oxidative and lipotoxic damage remains unknown. Here, we studied the effects of γ-conglutin on cell death provoked by hydrogen peroxide and palmitate in HepG2 hepatocytes and insulin-producing MIN6 cells, and if a modulation of mitochondrial potential and reactive oxygen species (ROS) levels was involved. We also investigated how γ-conglutin influences insulin secretion and electrical activity of β-cells. The increased apoptosis of HepG2 cells exposed to hydrogen peroxide was prevented by γ-conglutin, and the viability and ROS content in γ-conglutin-treated cells was similar to that of non-exposed cells. Additionally, γ-conglutin partially protected MIN6 cells against hydrogen peroxide-induced death. This was associated with a marked reduction in ROS. No significant changes were found in the mitochondrial potential of γ-conglutin-treated cells. Besides, we observed a partial protection against lipotoxicity only in hepatocytes. Unexpectedly, we found a transient inhibition of insulin secretion, plasma membrane hyperpolarization, and higher KATP channel currents in β-cells treated with γ-conglutin. Our data show that γ-conglutin protects against cell death induced by oxidative stress or lipotoxicity by decreasing ROS and might also indicate that γ-conglutin promotes a β-cell rest, which could be useful for preventing β-cell exhaustion in chronic hyperglycemia.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2021.07.088