Liver autophagy contributes to the maintenance of blood glucose and amino acid levels
Liver autophagy contributes to the maintenance of blood glucose and amino acid levels
复制标题
DOI：
10.4161/auto.7.7.15371
复制
发表时间：
2011-07-01
期刊：
影响因子：
13.3
通讯作者：
Ueno, Takashi
中科院分区：
文献类型：
--
作者：
Ezaki, Junji;Matsumoto, Naomi;Ueno, Takashi
饥饿诱导的自噬释放的氨基酸的抑制和抑制对于细胞存活是必不可少的，但它们在成年动物中的实际代谢贡献知之甚少。在此，我们报告，在小鼠中，肝脏自噬通过将氨基酸转化为葡萄糖，从而对血糖的维持做出了显着贡献。在同步禁食启动方案下，在稳定的胰高血糖素水平存在下，自噬伴随着血浆胰岛素的下降而诱导，导致稳健的氨基酸释放。在肝脏特异性自噬（Atg 7）缺陷小鼠中，与野生型小鼠相比，没有发生氨基酸释放，血糖水平继续降低。丝氨酸（30毫克/动物）的管理发挥了相当的效果，提高血糖水平在饥饿下的对照野生型和突变小鼠。因此，缺乏由自噬蛋白水解释放的氨基酸是血糖降低的主要原因。在对照野生型肝脏自噬氨基酸释放显着抑制了先前的葡萄糖，这引起了迅速增加血浆胰岛素水平。这表明胰岛素在控制肝脏自噬中比胰高血糖素起主导作用。这些结果首次表明肝脏特异性自噬在血糖调节中起作用。
Both anabolism and catabolism of the amino acids released by starvation-induced autophagy are essential for cell survival, but their actual metabolic contributions in adult animals are poorly understood. Herein, we report that, in mice, liver autophagy makes a significant contribution to the maintenance of blood glucose by converting amino acids to glucose via gluconeogenesis. Under a synchronous fasting-initiation regimen, autophagy was induced concomitantly with a fall in plasma insulin in the presence of stable glucagon levels, resulting in a robust amino acid release. In liver-specific autophagy (Atg7)-deficient mice, no amino acid release occurred and blood glucose levels continued to decrease in contrast to those of wild-type mice. Administration of serine (30 mg/animal) exerted a comparable effect, raising the blood glucose levels in both control wild-type and mutant mice under starvation. Thus, the absence of the amino acids that were released by autophagic proteolysis is a major reason for a decrease in blood glucose. Autophagic amino acid release in control wild-type livers was significantly suppressed by the prior administration of glucose, which elicited a prompt increase in plasma insulin levels. This indicates that insulin plays a dominant role over glucagon in controlling liver autophagy. These results are the first to show that liver-specific autophagy plays a role in blood glucose regulation.