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Protein kinase B/Akt signalling is required for palmitate‐induced β‐cell lipotoxicity
Author(s) -
Higa M.,
Shimabukuro M.,
Shimajiri Y.,
Takasu N.,
Shinjyo T.,
Inaba T.
Publication year - 2006
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2005.00488.x
Subject(s) - lipotoxicity , protein kinase b , microbiology and biotechnology , signalling , beta (programming language) , protein kinase a , chemistry , kinase , signal transduction , biology , endocrinology , computer science , insulin resistance , insulin , programming language
Aim: This study was conducted to clarify cell death and survival signals in pancreatic β‐cell lipotoxicity. Methods: Rat insulinoma INS‐1 cells, with or without expression of dominant‐negative mutant of Akt (K179M), were cultured with palmitate (C16:0) or oleate (C18:1) and cell numbers were determined by 0.2% eosin dye exclusion assay. The Akt activity was determined by anti‐3′‐phospho‐inositide‐dependent protein kinase (Akt)/protein kinase B (PKB) or anti‐phospho‐Akt (Serine 473) immunoblotting, and nuclear protein nuclear factor‐kB (NF‐κB)‐binding activity was by supershift analysis. Results: Twenty‐four hours treatment with palmitate increased the INS‐1 cell number at 0.1–0.2 m m but decreased the cell number at 0.5–1 m m . Oleate did not affect cell number at 0.1–1.0 m m . Palmitate dose‐dependently increased phosphorylation of 473th serine in Akt/PKB. The K179M form of Akt/PKB abolished palmitate‐induced cell proliferation at the low dose and death at the high dose. Nuclear protein NF‐κB binding was enhanced at 0.2 and 0.5 m m of palmitate but decreased at 1.0 m m . Conclusion: Results suggest that Akt/PKB signalling is involved in palmitate‐induced cell death and survival of pancreatic β cell.