Dietary protein deprivation upregulates insulin signaling and inhibits gluconeogenesis in rat liver
Dietary protein deprivation upregulates insulin signaling and inhibits gluconeogenesis in rat liver
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DOI：
10.1677/jme-10-0102
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发表时间：
2010-11-01
影响因子：
3.5
通讯作者：
Takahashi, Shin-Ichiro
中科院分区：
文献类型：
--
作者：
Toyoshima, Yuka;Tokita, Reiko;Takahashi, Shin-Ichiro
本研究旨在探讨膳食蛋白质剥夺对大鼠糖代谢和肝脏胰岛素信号转导的影响。用12%酪蛋白饮食（12 C）和无蛋白饮食（PF）喂养的大鼠的葡萄糖和丙酮酸耐量试验结果表明，蛋白质剥夺增强了血糖的清除并抑制了新生儿的发生。相应地，肝脏磷酸烯醇式丙酮酸羧激酶的mRNA水平，一个关键的促凋亡酶，抑制饮食蛋白质剥夺。在PF喂养的大鼠中，胰岛素注射诱导的肝脏中胰岛素受体（IR）的总酪氨酸磷酸化与12 C对喂养的大鼠相比增强，由于IR蛋白水平的增加。此外，蛋白剥夺引起IR底物1（IRS 1）和IRS 2蛋白水平的增加，导致胰岛素诱导的IRS 2酪氨酸磷酸化及其与磷脂酰肌醇3-激酶（PI 3 K）p85调节亚基的结合显著增强。基于这些结果，我们得出结论，蛋白质剥夺抑制胰岛素信号通过IR/IRS/PI 3 K/哺乳动物雷帕霉素复合物1通路在肝脏中的增强介导的机制。与我们以前的报告一起，这些研究结果表明，组织特异性增强胰岛素在肝脏和骨骼肌中的作用在维持葡萄糖稳态中起着重要作用，即使当能量使用减少膳食蛋白质剥夺。分子内分泌学杂志（2010）45，329-340
This study was undertaken to elucidate the effects of dietary protein deprivation on glucose metabolism and hepatic insulin signaling in rats. The results of glucose and pyruvate tolerance tests in rats fed with a 12% casein diet (12C) and a protein-free diet (PF) indicated that protein deprivation enhanced clearance of blood glucose and suppressed gluconeogenesis. Correspondingly, the mRNA level of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme, was suppressed by dietary protein deprivation. In PF-fed rats, total tyrosine phosphorylation of insulin receptor (IR) in the liver induced by insulin injection was enhanced compared with 12C pair-fed rats due to an increase in IR protein level. In addition, protein deprivation caused an increase in protein levels of IR substrate 1 (IRS1) and IRS2, leading to the marked enhancement of insulin-induced tyrosine phosphorylation of IRS2 and its binding to the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K). Based on these results, we conclude that protein deprivation suppresses gluconeogenesis by a mechanism primarily mediated by the enhancement of the insulin signals through the IR/IRS/PI3K/mammalian target of rapamycin complex 1 pathway in the liver. Taken together with our previous report, these findings suggest that tissue-specific potentiation of insulin action in the liver and the skeletal muscle plays important roles in maintaining glucose homeostasis even when energy usage is reduced by dietary protein deprivation. Journal of Molecular Endocrinology (2010) 45, 329-340