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KMID : 1200020200440060919
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Diabetes & Metabolism Journal
2020 Volume.44 No. 6 p.919 ~ p.927
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Hypoxia Increases β-Cell Death by Activating Pancreatic Stellate Cells within the Islet
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Kim Jong-Jin
Lee Esder
Ryu Gyeong-Ryul
Ko Seung-Hyun
Ahn Yu-Bae
Song Ki-Ho
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Abstract
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Background: Hypoxia can occur in pancreatic islets in type 2 diabetes mellitus. Pancreatic stellate cells (PSCs) are activated during hypoxia. Here we aimed to investigate whether PSCs within the islet are also activated in hypoxia, causing β-cell injury.
Methods: Islet and primary PSCs were isolated from Sprague Dawley rats, and cultured in normoxia (21% O2) or hypoxia (1% O2). The expression of α-smooth muscle actin (α-SMA), as measured by immunostaining and Western blotting, was used as a marker of PSC activation. Conditioned media (hypoxia-CM) were obtained from PSCs cultured in hypoxia.
Results: Islets and PSCs cultured in hypoxia exhibited higher expressions of α-SMA than did those cultured in normoxia. Hypoxia increased the production of reactive oxygen species. The addition of N-acetyl-L-cysteine, an antioxidant, attenuated the hypoxia-induced PSC activation in islets and PSCs. Islets cultured in hypoxia-CM showed a decrease in cell viability and an increase in apoptosis.
Conclusion: PSCs within the islet are activated in hypoxia through oxidative stress and promote islet cell death, suggesting that hypoxia-induced PSC activation may contribute to β-cell loss in type 2 diabetes mellitus.
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KEYWORD
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Hypoxia, Insulin-secreting cells, Islets of Langerhans, Oxidative stress, Pancreatic stellate cells
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