Selenium and diabetes--evidence from animal studies.

Selenium and diabetes--evidence from animal studies.
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DOI:
10.1016/j.freeradbiomed.2013.07.012
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发表时间:
2013-12
影响因子:
7.4
通讯作者:
Lei, Xin Gen
Lei, Xin Gen
中科院分区:
医学1区
文献类型:
--
作者:
Zhou, Jun;Huang, Kaixun;Lei, Xin Gen

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虽然硒被发现作为一种胰岛素模拟物,并在早期的研究中是抗糖尿病,最近的动物实验和人体试验表明,意想不到的风险,长期高硒摄入增强胰岛素抵抗和2型糖尿病。提高膳食硒摄入量(0.4至3.0毫克/公斤的饮食)以上的营养需求,类似于硒蛋白的过度生产,导致胰岛素抵抗和(或)糖尿病样表型的小鼠,大鼠和猪。虽然其致糖尿病的机制尚不清楚,但高硒摄入增加了包括GPx 1,MsrB 1,SelS和SelP在内的硒蛋白的活性或产生。这种上调减少了细胞内活性氧(ROS),然后使β细胞和胰岛素合成和分泌的关键调节因子失调,导致慢性高胰岛素血症。过清除细胞内H2 O2也衰减蛋白酪氨酸磷酸酶的氧化抑制和抑制胰岛素信号。高硒摄入可能影响糖酵解、脂肪生成和脂肪生成关键调节因子的表达和(或)功能。未来的研究是必要的,以找出某些形式的硒代谢物,除了硒蛋白,如果机制以外的细胞内氧化还原控制介导的高硒摄入量的致糖尿病作用。此外,高硒摄入量在癌症和糖尿病发生的中间阶段的潜在相互作用,应探讨使硒在人类营养和健康的最佳利用。
Whereas selenium was found to act as an insulin-mimic and to be anti-diabetic in earlier studies, recent animal experiments and human trials have shown unexpected risk of prolonged high Se intake in potentiating insulin resistance and type 2 diabetes. Elevating dietary Se intakes (0.4 to 3.0 mg/kg of diet) above the nutrient requirements, similar to overproduction of selenoproteins, led to insulin resistance and(or) diabetes-like phenotypes in mice, rats, and pigs. Although its diabetogenic mechanism remains unclear, the high Se intake elevated activity or production of selenoproteins including GPx1, MsrB1, SelS, and SelP. This up-regulation diminished intracellular reactive oxygen species (ROS) and then dys-regulated key regulators of β cells and insulin synthesis and secretion, leading to chronic hyperinsulinaemia. Over-scavenging intracellular H2O2 also attenuated oxidative inhibition of protein tyrosine phosphatases and suppressed insulin signaling. High Se intake might affect expression and(or) function of key regulators for glycolysis, gluconeogenesis, and lipogenesis. Future research is needed to find out if certain forms of Se metabolites in addition to selenoproteins and if mechanisms other than intracellular redox control mediate the diabetogenic effect of high Se intakes. Furthermore, a potential interactive role of high Se intakes in the interphase of carcinogenesis and diabetogenesis should be explored to make the optimal use of Se in human nutrition and health.
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