Jurnal

Palmitate induces reactive oxygen species production and b-cell dysfunction by activating nicotinamide adenine dinucleotide phosphate oxidase through Src signaling

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Aims/Introduction: Chronic hyperlipidemia impairs pancreatic b-cell function, referred to as lipotoxicity. We have reported an important role of endogenous reactive oxygen species (ROS) overproduction by activation of Src, a non-receptor tyrosine kinase, in impaired glucose-induced insulin secretion (GIIS) from diabetic rat islets. In the present study, we investigated the role of ROS production by Src signaling in palmitate-induced dysfunction of b-cells. Materials and Methods: After rat insulinoma INS-1D cells were exposed to 0.6 mmol/L palmitate for 24 h (palmitate exposure); GIIS, ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity were examined with or without exposure to10 lmol/L 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine (PP2), a Src inhibitior, for 30 or 60 min. Results: Exposure to PP2 recovered impaired GIIS and decreased ROS overproduction as a result of palmitate exposure. Palmitate exposure increased activity of NOX and protein levels of NOX2, a pathological ROS source in b-cells. Palmitate exposure increased the protein level of p47phox, a regulatory protein of NOX2, in membrane fraction compared with control, which was reduced by PP2. Transfection of small interfering ribonucleic acid of p47phox suppressed the augmented p47phox protein level in membrane fraction, decreased augmented ROS production and increased impaired GΙIS by palmitate exposure. In addition, exposure to PP2 ameliorated impaired GIIS and decreased ROS production in isolated islets of KK-Ay mice, an obese diabetic model with hyperlipidemia. Conclusions: Activation of NOX through Src signaling plays an important role in ROS overproduction and impaired GΙIS caused by chronic exposure to palmitate, suggesting a lipotoxic mechanism of b-cell dysfunction of obese mice.

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Detail Information

Series Title

JDI Jurnal of Diabetes Investigation Volume 5, Issue 1 January 2014

Call Number

(05) 616.46 WIL j

Publisher

Australia : Wiley., 2014

Collation

Hlm. 19-26

Language

English

ISBN/ISSN

2040-1124

Classification

(05) 616.46 WIL j

Content Type

-

Media Type

-

Carrier Type

-

Edition

Volume 5, Issue 1

Subject(s)

Lipotoxicity
Pancreatic b-cells
Reactive oxygen species

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