Korean Diabetes Journal 2002;26(3):179-187.
Published online June 1, 2002.
Effects of Antioxidants on Ethidium Bromide-induced Inhibition of Insulin Secretion in Rat Pancreatic Islets.
Chul Hee Kim, Chan Hee Kim, Hyeong Kyu Park, Kyo Il Suh, Ki Up Lee
1Department of Internal Medicine, Soonchunhyang University College of Medicine, Korea.
2Asan Institute for Life Sciences, Korea.
3Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea.
Abstract
BACKGROUND
It was recently shown that mitochondrial function in pancreatic beta-cells is essential in nutrient-stimulated insulin secretion. The inhibition of mitochondrial DNA (mtDNA) transcription by ethidium bromide (EtBr) has been reported to suppress glucose-induced insulin secretion in beta-cell lines. This study was undertaken to examine the effects of EtBr on insulin secretion in isolated normal rat pancreatic islets, and to see whether antioxidants could protect the beta-cell function against the EtBr-induced impairment. METHODS: Pancreatic islets of normal Sprague-Dawley rats were isolated by intraductal injection of collagenase followed by Ficoll-gradient centrifugation. Isolated islets were treated with 0.2 +/- 2.0 microgram/mL of EtBr for 2 to 6 days, and the glucose-stimulated insulin secretion measured. The effects of the antioxidant, vitamin E and alpha-lipoic acid, on the EtBr-induced inhibition of insulin secretion were also examined. RESULTS: EtBr inhibited the basal and glucose-stimulated insulin secretion in normal rat pancreatic islets in a dose- and time-dependent manner. Vitamin E and alpha-lipoic acid prevented the EtBr-induced inhibition of insulin secretion. CONCLUSION: Our results show that antioxidant can protect normal rat pancreatic islets from the EtBr-induced inhibition of insulin secretion. This suggests that oxidative stress is involved in the pathogenesis of the insulin secretory defect associated with mitochondrial dysfunction.
Key Words: Insulin secretion, Ethidium bromide, Mitochondrial DNA, Antioxidant, Rat pancreatic islets


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