|
KMID : 0354720060300040246
|
|
Journal of Korean Diabetes Association
2006 Volume.30 No. 4 p.246 ~ p.253
|
|
|
Glucose Oxidation and Production of Reactive Oxygen Species (ROS) in INS-1 Cells and Rat Islet Cells Exposed to High Glucose
|
|
Yoon Ji-Sung
Won Kyu-Chang
Lee Hyung-Woo
|
|
|
Abstract
|
|
|
Background: Chronic exposure of pancreatic islets to supraphysiologic concentrations of glucose causes beta cell dysfunction that is a process known as glucose toxicity. It has been reported that hyperglycemia increases the production of reactive oxygen species (ROS) in human islets and that ROS accumulation causes beta cell dysfunction associated with low capacity of intrinsic antioxidant enzymes. Also it has been postulated that this increase in ROS is prevented by an inhibitor of electron transport chain complex. The purpose of this study were to determine whether prolonged exposure of pancreatic islets to supraphysiologic glucose concentrations disrupts the intracellular balance between ROS thereby causing defective insulin secretion and to evaluate the site of hyperglycemia-induced ROS production.
Methods: INS-1 cells & rat islets were incubated in increasing concentrations of glucose and either an inhibitor of complex I & II (TTFA), an uncoupler of oxidative phosphorylation (CCCP), aCCA, etc and also incubated in increasing concentration of glyceraldehyde and N-acetylcystein. Then intracellular peroxide levels by flow cytometric analysis and glucose induced insulin secretion were detected.
Results: We observed that incubation with 30 mM glucose increased intracellular peroxide levels but decreased glucose-stimulated insulin secretion (GSIS) (P < 0.05). Exposure to TTFA, CCCP, aCCA did not reduce this increased intracellular peroxide levels, and did not increase GSIS (P < 0.05). 24-h incubation with glyceraldehyde at 5.6 mM glucose increased intracellular peroxide levels and decreased insulin content.
Conclusion: These observations indicate that there might be other origins in which ROS species are produced besides electron transport chain in mitochondria and glyceraldehyde may be a key molecule to produce ROS, and induce beta cell dysfunction.
|
|
|
KEYWORD
|
|
|
Diabetes Mellitus, Glucose toxicity, Glyceraldehyde, Oxidative stress, Reactive oxygen species
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|