Zhu Y, Goodridge A G, Stapleton S R
Department of Chemistry, Western Michigan University, Kalamazoo 49008.
Biochem J. 1994 Oct 1;303 ( Pt 1)(Pt 1):213-6. doi: 10.1042/bj3030213.
Insulin regulates the expression of genes involved in a variety of metabolic processes. In chick-embryo hepatocytes in culture, insulin amplifies the tri-iodothyronine (T3)-induced enzyme activity, and the level and rate of transcription of mRNA for both fatty acid synthase (FAS) and malic enzyme (ME). Insulin alone, however, has little or no effect on the expression of these genes. In chick-embryo hepatocytes, the mechanism by which insulin regulates the expression of these or other genes is not known. Several recent studies have compared the effects of zinc, vanadate and selenate on insulin-sensitive processes in an attempt to probe the mechanism of insulin action. Because zinc, vanadate and selenate mimic the effects of insulin on several processes, they have been termed insulin-mimetics. We have studied the effect of zinc, vanadate and selenate on the T3-induced expression of both FAS and ME. Like insulin, these agents had little or no effect on the basal activities for FAS and ME in chick-embryo hepatocytes in culture for 48 h. Unlike insulin, however, zinc, vanadate and selenate inhibited the T3-induced activities and mRNA levels of both FAS and ME. Maximal inhibition was achieved at concentrations of 50 microM zinc or vanadate, or 20 microM selenate. Zinc and vanadate also inhibited the T3-induced transcription of the FAS and ME genes. Although the mechanism of this inhibition is unknown, our results indicate that it is not mediated through inhibition of binding of T3 to its nuclear receptor nor through a general toxic effect. Thus zinc, vanadate and selenate are not insulin-mimetics under all conditions, and their effects on other insulin-sensitive processes may be fortuitous and unrelated to actions or components of the insulin signalling pathway.
胰岛素调节参与多种代谢过程的基因表达。在培养的鸡胚肝细胞中，胰岛素可增强三碘甲状腺原氨酸（T3）诱导的酶活性，以及脂肪酸合酶（FAS）和苹果酸酶（ME）的mRNA水平和转录速率。然而，单独的胰岛素对这些基因的表达几乎没有影响。在鸡胚肝细胞中，胰岛素调节这些或其他基因表达的机制尚不清楚。最近的几项研究比较了锌、钒酸盐和硒酸盐对胰岛素敏感过程的影响，试图探究胰岛素作用的机制。由于锌、钒酸盐和硒酸盐在几个过程中模拟了胰岛素的作用，它们被称为胰岛素模拟物。我们研究了锌、钒酸盐和硒酸盐对T3诱导的FAS和ME表达量的影响。与胰岛素一样，这些试剂对培养48小时的鸡胚肝细胞中FAS和ME的基础活性几乎没有影响。然而，与胰岛素不同的是，锌、钒酸盐和硒酸盐抑制了T3诱导的FAS和ME活性以及mRNA水平。在50 microM锌或钒酸盐或20 microM硒酸盐的浓度下可实现最大抑制。锌和钒酸盐还抑制了T3诱导的FAS和ME基因的转录。虽然这种抑制的机制尚不清楚，但我们的结果表明，它不是通过抑制T3与其核受体的结合介导的，也不是通过一般的毒性作用介导的。因此，锌、钒酸盐和硒酸盐在所有条件下都不是胰岛素模拟物，它们对其他胰岛素敏感过程的影响可能是偶然的，与胰岛素信号通路的作用或成分无关。
