Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide.
Oxidative stress is induced under diabetic conditions and possibly causes various forms of tissue damage in patients with diabetes. Recently, it has become aware that susceptibility of pancreatic beta-cells to oxidative stress contributes to the progressive deterioration of beta-cell function in type 2 diabetes. A hypoglycemic sulfonylurea, gliclazide, is known to be a general free radical scavenger and its beneficial effects on diabetic complications have been documented. In the present study, we investigated whether gliclazide could protect pancreatic beta-cells from oxidative damage. One hundred and fifty microM hydrogen peroxide reduced viability of mouse MIN6 beta-cells to 29.3%. Addition of 2 microM gliclazide protected MIN6 cells from the cell death induced by H(2)O(2) to 55.9%. Glibenclamide, another widely used sulfonylurea, had no significant effects even at 10 microM. Nuclear chromatin staining analysis revealed that the preserved viability by gliclazide was due to inhibition of apoptosis. Hydrogen peroxide-induced expression of an anti-oxidative gene heme oxygenase-1 and stress genes A20 and p21(CIP1/WAF1), whose induction was suppressed by gliclazide. These results suggest that gliclazide reduces oxidative stress of beta-cells by H(2)O(2) probably due to its radical scavenging activity. Gliclazide may be effective in preventing beta-cells from the toxic action of reactive oxygen species in diabetes.
Kimoto
Kiyoko
K
Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, Mitaka, Tokyo 181-8611, Japan.
Suzuki
Kenji
K
Kizaki
Takako
T
Hitomi
Yoshiaki
Y
Ishida
Hitoshi
H
Katsuta
Hidenori
H
Itoh
Eisuke
E
Ookawara
Tomomi
T
Suzuki
Keiichiro
K
Honke
Koichi
K
Ohno
Hideki
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005907:Gliclazide / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species
D000975:Antioxidants; D002843:Chromatin; D018076:DNA, Complementary; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012313:RNA; D004247:DNA; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005907:Gliclazide