Molecular Mechanism of Induction of Key Enzymes Related to Lipogenesis
Molecular Mechanism of Induction of Key Enzymes Related to Lipogenesis
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脂肪生成相关关键酶诱导的分子机制
DOI：
10.3181/00379727-200-43419
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发表时间：
1992
影响因子：
--
通讯作者：
Takehiko Tanaka
中科院分区：
文献类型：
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作者：
T. Noguchi;N. Iritani;Takehiko Tanaka
肝脏中与脂肪生成相关的关键酶可由高糖饮食或胰岛素诱导，并可由饥饿、糖尿病或胰高血糖素抑制。这些酶中的大多数也可由膳食果糖诱导，甚至在糖尿病肝脏中也是如此。这种调控发生在转录后水平和转录水平。我们广泛研究了l型丙酮酸激酶（LPK）诱导的分子机制。肝脏中LPK基因的转录受到胰岛素的刺激和胰高血糖素的抑制。这种胰岛素作用需要持续的蛋白质合成和葡萄糖代谢，并通过糖皮质激素增强。另一方面，果糖诱导LPK的机制依赖于血浆胰岛素水平。饮食中的果糖在正常大鼠中刺激LPK基因的转录，而在糖尿病大鼠中主要在转录后水平起作用。这些果糖效应可归因于果糖和甘油的共同代谢物。在肥胖型非胰岛素依赖型糖尿病模型Wistar肥胖大鼠的肝脏中，膳食葡萄糖对LPK mRNA的诱导作用受到损害，但果糖诱导的LPK mRNA的积累并未受到影响。对转基因小鼠的研究表明，LPK基因的5 ' -侧翼区域高达- 3kb，包含了LPK组织特异性表达以及饮食和胰岛素刺激所必需的所有c/s作用元件。利用瞬时表达法进一步分析发现，在- 170 kb范围内的肝细胞中存在三个c/s作用元件，这些元件是LPK表达所必需的。然而，当对转基因小鼠进行分析时，这些元素单独不足以调节这种酶的饮食和激素。
Abstract Key enzymes related to lipogenesis in the liver are induced by a high glucose diet or insulin and suppressed by starvation, diabetes, or glucagon. Most of these enzymes are also induced by dietary fructose, even in diabetic liver. This regulation occurs at the posttranscriptional level as well as at the transcriptional level. We studied extensively the molecular mechanism of induction of L-type pyruvate kinase (LPK). The transcription of the LPK gene in the liver was stimulated by insulin and inhibited by glucagon. This insulin action required ongoing protein synthesis and metabolism of glucose and was enhanced by glucocorticoid. On the other hand, the mechanism of induction of the LPK by dietary fructose depended on plasma insulin levels. Dietary fructose stimulated transcription of the LPK gene in normal rats, whereas it acted mainly at the posttranscriptional level in diabetic rats. These fructose effects were attributable to a common metabolite of fructose and glycerol. The induction of LPK mRNA by dietary glucose was impaired in the liver of Wistar fatty rats, a model of obese non-insulin-dependent diabetes mellitus, but fructose-induced accumulation of the mRNA was not. Studies on transgenic mice indicated that the 5′-flanking region up to −3 kb of the LPK gene contained all c/s-acting elements necessary for tissue-specific expression of LPK and its stimulation by diets and insulin. Further analysis using a transient expression assay revealed the presence of three c/s-acting elements necessary for expression of LPK in hepatocytes in the region up to −170 kb. However, these elements alone were not sufficient for dietary and hormonal regulation of this enzyme when analyzed in transgenic mice.
转基因小鼠中大鼠丙酮酸激酶L/氯霉素乙酰转移酶融合基因的组织特异性表达及其饮食和胰岛素的调节。
DOI：
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发表时间：
1990
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
K. Yamada;T. Noguchi;J. Miyazaki;T. Matsuda;M. Takenaka;K. Yamamura;T. Tanaka
通讯作者：
T. Tanaka