Sulfonylurea as well as elevated glucose levels stimulate reactive oxygen species production in the pancreatic β-cell line, MIN6-a role of NAD(P)H oxidase in β-cells

Hirotaka Tsubouchi, Toyoshi Inoguchi, Mieko Inuo, Maiko Kakimoto, Toshiyo Sonta, Noriyuki Sonoda, Shuji Sasaki, Kunihisa Kobayashi, Hideki Sumimoto, Hajime Nawata

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Increased oxidative stress may play a key role in the progressive deterioration of pancreatic β-cells and the development of diabetes. However, the underlying mechanism is not well understood. Exposure of pancreatic β-cell line, MIN6 cells, to elevated glucose level for 2 h induced an increase in reactive oxygen species (ROS) production, as evaluated by the staining of 2′,7′-dichlorofluorescein diacetate. This effect was completely blocked by NAD(P)H oxidase inhibitor (diphenylene iodonium) and protein kinase C (PKC) inhibitor (calphostin C), but not affected by other flavoprotein inhibitors (rotenone, oxypurinol, or l-N-monomethyl arginine). Glibenclamide also stimulated ROS production in a dose-dependent manner. This effect was again blocked by diphenylene iodonium and calphostin C. In conclusion, insulin secretagogues, both glibenclamide and elevated glucose level, stimulated ROS production in β-cells through a PKC-dependent activation of NAD(P)H oxidase. This mechanism may be a novel therapeutic target for preventing the progression of β-cell deterioration.

Original languageEnglish
Pages (from-to)60-65
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume326
Issue number1
DOIs
Publication statusPublished - Dec 31 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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