亚硒酸钠提高青春期大鼠胰岛素敏感性的作用途径

目的 探讨亚硒酸钠改善青春期胰岛素抵抗大鼠胰岛素敏感性的细胞机制。方法 以高脂饮食制备的青春期胰岛素抵抗大鼠模型离体肝细胞为研究对象,分别用阴离子交换树脂层析法和RT-PCR法检测肝细胞肌醇三磷酸(IP3)含量、磷脂酰肌醇3-激酶p85α亚基(P13Kp85α)mRNA和硒蛋白P(Se-P)mRNA表达量,同时观察体内外补硒对上述指标的影响。结果 青春期胰岛素抵抗大鼠离体肝细胞Se-P mRNA、P13Kp85αmRNA表达量和IP3含量均降低,以前两者更加明显;补硒组大鼠肝细胞Se-P mRNA水平升高,P13Kp85αmRNA和IP3达正常组水平;在胰岛素刺激下,补硒组大鼠肝细胞P13Kp85αmRNA和IP3水平与正常组相似,均较单纯高脂组明显改善;P13K特异性抑制剂wortmannin抑制后,补硒组肝细胞IP3水平虽然升高,但仍低于正常组水平。结论亚硒酸钠改善青春期胰岛素抵抗大鼠的胰岛素敏感性,可能与改善肌醇磷脂P13K信号通路有关,而对IP3水平的调节作用不及胰岛素。

Cell biological mechanism involved in the effect of sodium selenite on improving insulin sensitivity

OBJECTIVE: To study the cell biological mechanism of sodium selenite improving insulin sensitivity in pubertal rats with insulin resistance. METHODS: The content of inositol 1,4,5-trisphosphate (IP3) was examined by anion resin chromatography, and mRNA levels of phosphatidylinositol 3-kinase regulatory subunits (PI3Kp85 alpha) and Se-P were detected by RT-PCR in hepatocyte isolated from pubertal rats with insulin resistance. RESULTS: The mRNA levels of Se-P and PI3Kp85 alpha and content of IP3 in isolated hepatocyte decreased in pubertal male rats with insulin resistance. The above indices increased and reached normal level in rats supplied with selenium. The response to insulin stimulation in isolated hepatocyte in rats with selenium supply was similar to that in the control group, and both groups had higher response than those with high-fat diet. Alone when inhibited by wortmannin, the concentration of IP3 increased slightly in rats with selenium supply, but still was lower than that in the control group. CONCLUSIONS: These results indicate that the effect of selenium improving insulin sensitivity may be related to phosphatidylinositol PI3K signalling pathway. The effect of regulation of IP3 by selenium is not as effective as that by insulin, which may explain the difference of effect between selenium and insulin.