TITLE

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

AUTHOR(S)
Caroline Kiaer; Peter Thams
PUB. DATE
June 2009
SOURCE
Endocrine (1355008X);Jun2009, Vol. 35 Issue 3, p325
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
40419545

 

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