Effects of redox interference on the pancreatic mitochondria and the abnormal blood glucose

Effects of redox interference on the pancreatic mitochondria and the abnormal blood glucose
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氧化还原干扰对胰腺线粒体及血糖异常的影响

DOI:
10.1080/10715762.2020.1866180
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发表时间:
2020-12
影响因子:
3.3
通讯作者:
Shi Dongyun
Shi Dongyun
中科院分区:
生物学3区
文献类型:
--
作者:
Xie Feizhou;Wu Meiling;Lai Ben;Halim Michael;Liu Shanlin;Shi Dongyun

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摘要活性氧簇(ROS)与糖尿病的发生和发展密切相关,但氧化还原状态对糖尿病的影响尚不完全清楚。在这里,我们研究氧化还原干扰对胰腺线粒体和糖尿病进展的作用。用链脲佐菌素(STZ)复制糖尿病(DM)大鼠模型,用FeSO4产生氧化应激(OS),用灵芝多糖作抗氧化干预(AO)。结果表明,在OS组和DM组,氧化应激导致氧化还原状态失衡,导致脂质过氧化水平升高,抗氧化水平降低,而AO治疗组通过修复氧化还原平衡而降低血糖。胰岛素水平顺序为正常对照组(NC)<AO < DM < OS,提示氧化应激以代偿机制促进胰岛素分泌。OS组胰腺组织中Mn-SOD的表达显著低于其他组,而P53的表达显著高于其他组。DM组胰腺β细胞线粒体超微结构受损,OS组损伤更重,与之平行的分泌颗粒明显减少,而AO组两者均得到修复。我们的结果表明,氧化还原状态可以影响糖尿病大鼠的血糖,氧化应激可以加重糖尿病,而早期的抗氧化治疗可以通过逆转氧化还原状态的失衡和修复胰腺线粒体来缓解糖尿病的进程。提示氧化还原平衡在糖尿病的治疗中起着重要作用。
Abstract Reactive oxygen species (ROS) has been implicated as a contributor to both the onset and the progression of diabetes, however how does redox state affect diabetes has not been fully understood. Here we study the role of redox interference on pancreatic mitochondria and the progression of diabetes. We applied streptozotocin (STZ) to establish diabetes mellitus (DM) model in rats, applied FeSO4 to produce oxidative stress (OS) and Ganoderma lucidum polysaccharides as antioxidant intervention (AO). Our results showed that in OS and DM group, oxidative stress caused the imbalance of redox state, resulting in higher lipid peroxidation level and lower antioxidant level, while AO treatment group reduced blood glucose by repairing the redox balance. The insulin level has the order of Normal Control (NC)<AO < DM < OS, suggesting oxidative stress promoted insulin secretion in a compensatory mechanism. The Mn-SOD expression in OS groups of pancreas were significantly lower than other groups, while the p53 expression was significantly higher. The mitochondrial ultrastructure of pancreatic β cells were impaired in DM group, and the damage was more severe in OS group, paralleled with significantly reduced secretory granules, both of which were repaired in the AO group. Our results demonstrated that the redox state can affect the blood glucose of diabetic rats, and oxidative stress can aggravate diabetes, while the early antioxidant treatment can alleviate the process of diabetes through reversing the imbalance of redox state and repairing the pancreatic mitochondria. These results suggest that redox balance plays an important role in the treatment of diabetes.
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