Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide.
Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide.
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发表时间：
2003
影响因子：
3.1
通讯作者：
K. Kimoto;Kenji Suzuki;T. Kizaki;Y. Hitomi;H. Ishida;Hidenori Katsuta;E. Itoh;T. Ookawara;Keiichiro Suzuki;K. Honke;H. Ohno
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作者：
K. Kimoto;Kenji Suzuki;T. Kizaki;Y. Hitomi;H. Ishida;Hidenori Katsuta;E. Itoh;T. Ookawara;Keiichiro Suzuki;K. Honke;H. Ohno
氧化应激是在糖尿病条件下诱导的，可能会导致糖尿病患者各种形式的组织损伤。最近，人们意识到胰岛β细胞对氧化应激的敏感性是2型糖尿病患者胰岛β细胞功能进行性恶化的原因之一。一种降血糖的磺脲类药物格列齐特被认为是一种广泛的自由基清除剂，其对糖尿病并发症的有益作用已有文献记载。在目前的研究中，我们研究了格列齐特是否可以保护胰岛β细胞免受氧化损伤。150微米过氧化氢使小鼠MIN6β细胞存活率降低至29.3%。加入2微米格列齐特对H(2)O(2)诱导的MIN6细胞死亡的保护作用为55.9%。格列本脲是另一种广泛使用的磺脲类药物，即使在10微米也没有显著效果。核染色质染色分析表明，格列齐特保存的存活率是由于抑制了细胞的凋亡。过氧化氢诱导的抗氧化基因血红素加氧酶-1和应激基因A20和p21(CIP1/WAF1)的表达，其诱导被格列齐特抑制。这些结果表明，格列齐特可通过H(2)O(2)减轻β细胞的氧化应激，其机制可能与其清除自由基有关。格列齐特可能有效地防止糖尿病中的β细胞免受活性氧的毒性作用。
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.