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Serum albumin protects from cytokine-induced pancreatic β cell death by a phosphoinositide 3-kinase-dependent mechanism

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Abstract

The present study was undertaken to investigate the biological activity of serum albumin when pancreatic β cells were challenged by cytokines and pro-apoptotic reactive oxygen species like H2O2. Culture of mouse islets or INS-1E β cells for 24 h in the presence of H2O2 (25 μmol/l) increased cell death. This demise was prevented by serum albumin, dependent on its free sulfhydryl group, emphasizing that albumin may scavenge H2O2 due to its antioxidant properties. Culture for 48 h with a cytokine mixture of IL-1β (160 pg/ml), IFN-γ (200 ng/ml), and TNF-α (2 ng/ml) revealed that albumin, also protected against cytokine-induced death of both mouse islets and INS-1E β cells. This protective effect against cytokine-induced β cell death was, however, not dependent on albumins free sulfhydryl group, but was inhibited by the phosphoinositide 3-kinase (PI3K) inhibitors LY294002 (25 μmol/l) and wortmannin (1 μmol/l), suggesting that albumin may rescue β cells from cytokine-induced cell death by activation of PI3K. In accordance, albumin stimulated phosphorylation of Akt, a down-stream target for PI3K. In conclusion, it is suggested that albumin may be a survival factor for pancreatic β cells through scavenging of reactive oxygen species and by PI3K-dependent activation of Akt.

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Acknowledgments

This work was supported by the Danish Diabetes Association, the Novo Nordic Foundation, the Medical Research Council, and the A. P. Møller Foundation for the Advancement of Medical Science. The skilful technical assistance of Bente Vinther and Susanne Johannessen is highly appreciated.

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  1. Department of Biomedical Sciences, University of Copenhagen, 3C Blegdamsvej, 2200, Copenhagen N, Denmark

    Caroline Kiaer & Peter Thams

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  1. Caroline Kiaer
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  2. Peter Thams
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Correspondence to Peter Thams.

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Kiaer, C., Thams, P. Serum albumin protects from cytokine-induced pancreatic β cell death by a phosphoinositide 3-kinase-dependent mechanism. Endocr 35, 325–332 (2009). https://doi.org/10.1007/s12020-009-9161-7

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  • DOI: https://doi.org/10.1007/s12020-009-9161-7

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