Beneficial effects of antioxidants in diabetes -: Possible protection of pancreatic β-cells against glucose toxicity
Beneficial effects of antioxidants in diabetes -: Possible protection of pancreatic β-cells against glucose toxicity
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DOI：
10.2337/diabetes.48.12.2398
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发表时间：
1999-12-01
期刊：
影响因子：
7.7
通讯作者：
Hori, M
中科院分区：
文献类型：
--
作者：
Kaneto, H;Kajimoto, Y;Hori, M
氧化应激是在糖尿病条件下产生的，并可能导致糖尿病患者各种形式的组织损伤。本研究的目的是研究氧化应激在2型糖尿病胰腺β细胞功能障碍进展中的作用，并评估抗氧化剂在2型糖尿病治疗中的潜在作用。我们使用糖尿病C57BL/KsJ-db/db小鼠，在6周龄时开始抗氧化治疗（n -乙酰- l-半胱氨酸[NAC]，维生素C加E，或两者兼有）；其效果仅在10周龄和16周龄时进行评估。根据腹腔内葡萄糖耐量试验，NAC治疗保留了葡萄糖刺激的胰岛素分泌，并适度降低了血糖水平。维生素C和E单独使用时没有效果，但与NAC联合使用时略有效果。给非糖尿病小鼠同样的抗氧化剂对胰岛素分泌没有影响。胰腺的组织学分析显示，抗氧化剂治疗的糖尿病小鼠的β细胞质量明显大于未治疗的小鼠。作为一种可能的原因，抗氧化处理抑制了β细胞的凋亡，但没有改变β细胞的增殖速度，这支持了慢性高血糖症中氧化应激诱导的凋亡导致β细胞质量减少的假设。抗氧化处理还保留了胰岛素含量和胰岛素mRNA的量，使胰岛素脱颗粒程度不明显。此外，抗氧化处理后胰岛细胞细胞核中β细胞特异性转录因子-胰腺和十二指肠同源盒因子-1 （PDX-1）的表达更加明显。总之，我们的观察表明，抗氧化治疗可以在保持体内β细胞功能的情况下对糖尿病发挥有益作用。这一发现表明抗氧化剂对治疗糖尿病有潜在的作用，并进一步支持了氧化应激在糖尿病β细胞功能障碍中的作用。
Oxidative stress is produced under diabetic conditions and possibly causes various forms of tissue damage in patients with diabetes. The aim of this study was to examine the involvement of oxidative stress in the progression of pancreatic beta-cell dysfunction in type 2 diabetes and to evaluate the potential usefulness of antioxidants in the treatment of type 2 diabetes. We used diabetic C57BL/KsJ-db/db mice, in whom antioxidant treatment (N-acetyl-L-cysteine [NAC], vitamins C plus E, or both) was started at 6 weeks of age; its effects mere evaluated at 10 and 16 weeks of age. According to an intraperitoneal glucose tolerance test, the treatment with NAC retained glucose-stimulated insulin secretion and moderately decreased blood glucose levels. Vitamins C and E were not effective when used alone but slightly effective when used in combination with NAC. No effect on insulin secretion was observed when the same set of antioxidants was given to nondiabetic control mice. Histologic analyses of the pancreases revealed that the beta-cell mass was significantly larger in the diabetic mice treated with the antioxidants than in the untreated mice. As a possible cause, the antioxidant treatment suppressed apoptosis in beta-cells without changing the rate of beta-cell proliferation, supporting the hypothesis that in chronic hyperglycemia, apoptosis induced by oxidative stress causes reduction of beta-cell mass. The antioxidant treatment also preserved the amounts of insulin content and insulin mRNA, making the extent of insulin degranulation less evident. Furthermore, expression of pancreatic and duodenal homeobox factor-1 (PDX-1), a beta-cell-specific transcription factor, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. In conclusion, our observations indicate that antioxidant treatment can exert beneficial effects in diabetes, with preservation of in vivo beta-cell function. This finding suggests a potential usefulness of antioxidants for treating diabetes and provides further support for the implication of oxidative stress in beta-cell dysfunction in diabetes.