Chromium(D-phenylalanine)3 supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice
Chromium(D-phenylalanine)3 supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice
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DOI：
10.1093/jn/138.10.1846
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发表时间：
2008-10-01
影响因子：
4.2
通讯作者：
Sreejayan, Nair
中科院分区：
文献类型：
--
作者：
Dong, Feng;Kandadi, Machender Reddy;Sreejayan, Nair
铬作为糖尿病和胰岛素抵抗受试者的营养补充剂已经得到普及。本研究旨在评价一种新型D-苯丙氨酸铬络合物[Cr（D-phe）（3）]对胰岛素抵抗、蔗糖喂养小鼠的长期给药效果。通过9周的蔗糖喂养在FVB小鼠中产生全身胰岛素抵抗，随后将它们随机分配为未补充IS组）或接受口服Cr（D-phe）3饮用水（SCr组），剂量为45 μ g.kg（-1）.d（-1）（类似于3.8 μ g元素chrornium.kg（-1）.d（-1））。对照组（C）不消耗蔗糖，也不补充蔗糖。与对照组相比，蔗糖喂养的小鼠血清胰岛素浓度升高，而接受Cr（D-phe）3的蔗糖喂养的小鼠血清胰岛素浓度显著降低，与对照组无差异。蔗糖喂养小鼠的葡萄糖耐量受损（通过腹膜内葡萄糖耐量试验后葡萄糖处置率差证明）在接受Cr（D-phe）的小鼠中得到显著改善（3）。补充铬显著增强胰岛素刺激的Akt磷酸化和膜相关葡萄糖转运蛋白-4在蔗糖喂养的小鼠骨骼肌。在培养的脂肪细胞中，由于长期暴露于高浓度的葡萄糖和胰岛素而导致胰岛素抵抗，Cr（D-phe）（3）增强Akt磷酸化和葡萄糖摄取。这些结果表明，饮食中补充Cr（D-phe）3可能对胰岛素抵抗的前驱糖尿病具有潜在的有益作用。
Chromium has gained popularity as a nutritional supplement for diabetic and insulin-resistant subjects. This study was designed to evaluate the effect of chronic administration of a novel chromium complex Of D-phenylalanine [Cr(D-phe)(3)]in insulin-resistant, sucrose-fed mice. Whole-body insulin resistance was generated in FVB mice by 9 wk of sucrose feeding, following which they were randomly assigned to be unsupplemented IS group) or to receive oral Cr(D-phe)3 in drinking water (SCr group) at a dose of 45 mu g.kg(-1).d(-1) (similar to 3.8 mu g of elemental chrornium.kg(-1).d(-1)). A control group (C) did not consume sucrose and was not supplemented. Sucrose-fed mice had an elevated serum insulin concentration compared with controls and this was significantly lower in sucrose-fed mice that received Cr(D-phe)3, which did not differ from controls. Impaired glucose tolerance in sucrose-fed mice, evidenced by the poor glucose disposal rate following an intraperitoneal glucose tolerance test, was significantly improved in mice receiving Cr(D-phe)(3). Chromium supplementation significantly enhanced insulin-stimulated Akt phosphorylation and membrane-associated glucose transporter-4 in skeletal muscles of sucrose-fed mice. In cultured adipocytes rendered insulin resistant by chronic exposure to high concentrations of glucose and insulin, Cr(D-phe)(3) augmented Akt phosphorylation and glucose uptake. These results indicate that dietary supplementation with Cr(D-phe)3 may have potential beneficial effects in insulin-resistant, prediabetic conditions.