TY - JOUR
T1 - 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
AU - Tsubouchi, Hirotaka
AU - Inoguchi, Toyoshi
AU - Inuo, Mieko
AU - Kakimoto, Maiko
AU - Sonta, Toshiyo
AU - Sonoda, Noriyuki
AU - Sasaki, Shuji
AU - Kobayashi, Kunihisa
AU - Sumimoto, Hideki
AU - Nawata, Hajime
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research (No. 16590888) from the Ministry of Education, Science and Culture, Japan. This work was carried out in part at Kyushu University Station for Collaborative Research.
PY - 2004/12/31
Y1 - 2004/12/31
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2004.10.201
DO - 10.1016/j.bbrc.2004.10.201
M3 - Article
C2 - 15567152
AN - SCOPUS:9644280976
SN - 0006-291X
VL - 326
SP - 60
EP - 65
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
