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

Abstract

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

Age‐related reduction and independent predictors of toe flexor strength in middle‐aged men

“…Inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α promote muscle atrophy [57]. Interestingly, in pancreatic β cells, albumin also positively regulates the PI3K-Akt signaling pathway, which protects against cytokine-induced β-cell death [56]. It is thus likely that a lower albumin level promotes diabetes-induced muscle weakness, followed by cytokine-induced impairment of insulin secretion in pancreas, and elevation of circulating glucose levels.…”

A critical role for CK2 in cytokine-induced activation of NFκB in pancreatic β cell death

“…The role of p38 MAP kinase in cytokine-induced β-cell death is, however, disputed, and some data suggest that cytokines may not activate p38 MAP kinase in pure β-cell populations [36]. Accordingly, the p38 MAP kinase inhibitor SB203580 did not prevent cytokine-induced β cell death in INS-1E β cells in this (results not given) and a previous study [24], suggesting that CK2 does not promote β cell death through cytokine activation of p38 MAP kinase.…”

“…Furthermore, ERK 1/2 may be activated by CK2 through phosphorylation of serines 244 and 246 [37]. In our hands, however, the ERK 1/2 MAP kinase inhibitor PD98059 did not inhibit cytokine-induced death of INS-1E β cells [24], suggesting that CK2 does not promote β cell death through cytokine activation of ERK 1/2 MAP kinase.…”

“…After 48 h of culture, the serum concentration was lowered to 0.5 % fetal calf serum for the remaining culture period with addition of cytokines [IL-1β (80 pg/ml), TNF-α (1 ng/ml), and IFN-γ (100 pg/ml)] and other test substances as specified in the text. This low concentration of serum did not affect cell viability [24]. …”

“…At the end of the incubation, the medium containing MTT was removed, and islets or cells were dissolved in DMSO. Absorbance was then measured at 540 and 690 nm [24]. …”