Lupi R, Del Guerra S, Mancarella R, Novelli M, Valgimigli L, Pedulli G F, Paolini M, Soleti A, Filipponi F, Mosca F, Boggi U, Del Prato S, Masiello P, Marchetti P
Dipartimento di Endocrinologia e Metabolismo, University of Pisa, Italy.
Diabetes Metab. 2007 Nov;33(5):340-5. doi: 10.1016/j.diabet.2007.03.005. Epub 2007 Jul 9.
Oxidative stress is a putative mechanism leading to beta-cell damage in type 2 diabetes. We studied isolated human pancreatic islets from type 2 diabetic and non-diabetic subjects, matched for age and body mass index. Evidence of increased oxidative stress in diabetic islets was demonstrated by measuring nitrotyrosine concentration and by electron paramagnetic resonance. This was accompanied by reduced glucose-stimulated insulin secretion, as compared to non-diabetic islets (Stimulation Index, SI: 0.9 +/- 0.2 vs. 2.0 +/- 0.4, P<0.01), and by altered expression of insulin (approximately -60%), catalase (approximately +90%) and glutathione peroxidase (approximately +140%). When type 2 diabetic islets were pre-exposed for 24 h to the new antioxidant bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate di-hydrochloride, nitrotyrosine levels, glucose-stimulated insulin secretion (SI: 1.6+/-0.5) and gene expressions improved/normalized. These results support the concept that oxidative stress may play a role in type 2 diabetes beta-cell dysfunction; furthermore, it is proposed that therapy with antioxidants could be an interesting adjunctive pharmacological approach to the treatment of type 2 diabetes.
氧化应激是导致2型糖尿病β细胞损伤的一种可能机制。我们研究了从2型糖尿病患者和非糖尿病患者中分离出的人胰岛，这些患者在年龄和体重指数上相匹配。通过测量硝基酪氨酸浓度和电子顺磁共振证明了糖尿病胰岛中氧化应激增加。与非糖尿病胰岛相比，这伴随着葡萄糖刺激的胰岛素分泌减少（刺激指数，SI：0.9±0.2对2.0±0.4，P<0.01），以及胰岛素（约-60%）、过氧化氢酶（约+90%）和谷胱甘肽过氧化物酶（约+140%）表达的改变。当2型糖尿病胰岛预先暴露于新的抗氧化剂双（1-羟基-2,2,6,6-四甲基-4-哌啶基）癸二酸二盐酸盐24小时后，硝基酪氨酸水平、葡萄糖刺激的胰岛素分泌（SI：1.6±0.5）和基因表达得到改善/恢复正常。这些结果支持氧化应激可能在2型糖尿病β细胞功能障碍中起作用的概念；此外，有人提出抗氧化剂治疗可能是治疗2型糖尿病的一种有趣的辅助药理学方法。
