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【medical-news】氧化应激的真面目:游离脂肪酸抑

Free Fatty Acid-Induced Reduction in Glucose Stimulated Insulin Secretion–Evidence for a Role of Oxidative Stress In Vitro and In Vivo

Objective: An important mechanism in the pathogenesis of type 2 diabetes in obese individuals is elevation of plasma FFA, which induce insulin resistance and chronically decrease ß-cell function and mass. Our objective was to investigate the role of oxidative stress in FFA-induced decrease in ß-cell function.

Research Design and Methods: We used an in vivo model of 48h i.v. oleate infusion in Wistar rats followed by hyperglycemic clamps, or islet secretion studies ex vivo, and in vitro models of 48h exposure to oleate in islets and MIN6 cells.

Results: 48h Infusion of oleate decreased the insulin and C-peptide responses to a hyperglycemic clamp (p<0.01), an effect prevented by coinfusion of the antioxidants N-acetylcysteine and taurine. Similar to the findings in vivo, 48h infusion of oleate decreased glucose stimulated insulin secretion ex vivo (p<0.01), and induced oxidative stress (p<0.001) in isolated islets, effects prevented by coinfusion of the antioxidants N-acetylcysteine, taurine, or tempol. 48h infusion of olive oil induced oxidative stress (p<0.001) and decreased the insulin response of isolated islets similar to oleate (p<0.01). Islets exposed to oleate or palmitate and MIN6 cells exposed to oleate showed a decreased insulin response to high glucose and increased levels of oxidative stress (both p<0.001), effects prevented by taurine. Real-time RT-PCR showed increased mRNA levels of antioxidant genes in MIN6 cells following oleate exposure, an effect partially prevented by taurine.

Conclusions: Our data are the first demonstration that oxidative stress plays a role in the decrease in ß-cell secretory function induced by prolonged exposure to FFA, in vitro and in vivo.

http://diabetes.diabetesjournals.org/cgi/content/abstract/db07-0075v2 本人已认领该文编译,48小时后若未提交译文,请其他战友自由认领 ________________________________________
Free Fatty Acid-Induced Reduction in Glucose Stimulated Insulin Secretion–Evidence for a Role of Oxidative Stress In Vitro and In Vivo
根据氧化应激在体内外的作用表明:游离脂肪酸引起了葡萄糖刺激的胰岛素分泌减少

Objective: An important mechanism in the pathogenesis of type 2 diabetes in obese individuals is elevation of plasma FFA, which induce insulin resistance and chronically decrease ß-cell function and mass. Our objective was to investigate the role of oxidative stress in FFA-induced decrease in ß-cell function.
目的:肥胖患者的2型糖尿病发病机制的一个重要环节是血清游离脂肪酸含量的增高,其导致了胰岛素抵抗以及ß细胞功能和数量的下降。我们实验的目的就是研究氧化应激在游离脂肪酸诱导的ß细胞功能减退中的作用。

Research Design and Methods: We used an in vivo model of 48h i.v. oleate infusion in Wistar rats followed by hyperglycemic clamps, or islet secretion studies ex vivo, and in vitro models of 48h exposure to oleate in islets and MIN6 cells.
研究设计与方法:我们将Wistar大鼠持续48小时静脉给入油酸,然后对其应用高糖钳夹来建立体内模型,或离体研究胰岛分泌,在体外模型中将胰岛和MIN6细胞暴露于油酸中达48小时。

Results: 48h Infusion of oleate decreased the insulin and C-peptide responses to a hyperglycemic clamp (p<0.01), an effect prevented by coinfusion of the antioxidants N-acetylcysteine and taurine.
结果:持续48小时注入油酸,降低了胰岛素和C肽对于高糖钳夹的反应程度(p<0.01),这一效应可以通过抗氧化剂N-乙酰半胱氨酸和牛磺酸的联合注射来预防。

Similar to the findings in vivo, 48h infusion of oleate decreased glucose stimulated insulin secretion ex vivo (p<0.01), and induced oxidative stress (p<0.001) in isolated islets, effects prevented by coinfusion of the antioxidants N-acetylcysteine, taurine, or tempol. 48h infusion of olive oil induced oxidative stress (p<0.001) and decreased the insulin response of isolated islets similar to oleate (p<0.01).
与体内研究的发现相似,离体条件下,持续48小时注入油酸降低了葡萄糖刺激的胰岛素分泌(p<0.01),并在离体的胰岛中引起了氧化应激(p<0.001),这一效应可以通过抗氧化剂N-乙酰半胱氨酸、牛磺酸或tempol(一种氮氧化物)的联合注射来预防。持续48小时注入橄榄油和注入油酸的结果相似,也引起了氧化应激(p<0.001)以及降低了离体胰岛的胰岛素反应。

Islets exposed to oleate or palmitate and MIN6 cells exposed to oleate showed a decreased insulin response to high glucose and increased levels of oxidative stress (both p<0.001), effects prevented by taurine.

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【文摘发布】NEJM 抑肽酶

作者:admin@医学,生命科学    2011-07-21 18:13
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