Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice
Insulin-independent induction of sterol regulatory element-binding protein-1c expression in the livers of streptozotocin-treated mice
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DOI：
10.2337/diabetes.53.3.560
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发表时间：
2004-03-01
期刊：
影响因子：
7.7
通讯作者：
Yamada, N
中科院分区：
文献类型：
--
作者：
Matsuzaka, T;Shimano, H;Yamada, N
胰岛素和葡萄糖共同调节肝脏类固醇调节元件结合蛋白(SREBP)-1c的表达。我们试图通过SREBP-1c的诱导，在糖和胰岛素的影响可以区分的情况下，探索脂肪生成的营养调控。为此，小鼠通过注射链脲佐菌素(STZ)耗尽胰岛素，并接受葡萄糖、果糖或蔗糖的空腹再喂养方案。出乎意料的是，胰岛素耗竭的小鼠表现出显著的SREBP-1c对所有糖的诱导，而且这种SREBP-1c的增加甚至比没有服用STZ的对照组更显著。在对照组和注射STZ的小鼠中，SREBP-1诱导变化的时间进程因糖的类型而异。葡萄糖再补饲对SREBP-1c的诱导达到峰值，而果糖再补给则缓慢而缓慢地增加，蔗糖再补给介于这两种反应之间。随着时间的推移，各种造脂酶的表达也逐渐增加，与糖的类型无关，注射STZ的小鼠的表达强度比未治疗的小鼠更强。相反，肝脏葡萄糖激酶的诱导和光烯醇式丙酮酸羧激酶的抑制在早期的REFED状态下依赖于胰岛素。这些数据清楚地表明，只要有足够的碳水化合物，SREBP-1c和造脂基因的营养调节可能完全不依赖于胰岛素。
Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought to explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects of sugars versus insulin could be distinguished. To do so, mice were insulin depleted by streptozotocin (STZ) administration and subjected to a fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, the insulin-depleted mice exhibited a marked induction of SREBP-1c on all sugars, and this increase in SREBP-1c was even more dramatic than in the non-STZ-administered controls. The time course of changes in SREBP-1 induction varied depending on the type of sugars in both control and STZ-administered mice. Glucose refeeding gave a peak of SREBP-1c induction, whereas fructose refeeding caused slow and gradual increments, and sucrose refeeding fell between these two responses. Expression of various lipogenic enzymes were also gradually increased over time, irrespective of the types of sugars, with greater intensities in STZ-administered than in nontreated mice. In contrast, induction of hepatic glucokinase and suppression of phoshoenolpyruvate carboxykinase were insulin dependent in an early refed state. These data clearly demonstrate that nutritional regulation of SREBP-1c and lipogenic genes may be completely independent of insulin as long as sufficient carbohydrates are available.