The molecular mechanism of insul in resistance induced by overnutrition

肝脏在氨基酸摄取和由氨基酸合成蛋白质以及一些胰岛素作用中起关键作用。p70核糖体蛋白激酶1（S6 K1）是翻译的关键调节因子，其过度活化通过对IRS 1的负反馈而诱导胰岛素抵抗。但其对S6 K1的调控作用尚不清楚。在这项研究中，我们假设Vps 34和Rheb作为营养传感器发挥mTOR-S6 K1信号传导的作用，并且GTP结合的Rheb诱导内体运输以激活mTOR。这些结果表明，Vps 34和Rheb，这是激活的营养摄取，调节S6 K1和Rheb的易位是至关重要的mTOR-S6 K1信号的激活。

Liver has the critical role in amino acids uptake and protein synthesis from amino acid as well as some insulin actions. p70 rebosomal protein kinase 1 (S6K1) is the key regulator of translation and its over activation induces insulin resistance by negative feedback to IRS1. However, its regulation of S6K1 has not be clear yet. In this study, we hypothesized that Vps34 and Rheb play a role of mTOR-S6K1 signaling as a nutrient sensor and GTP-bound Rheb induces endosome trafficking to activate mTOR. There results indicate Vps34 and Rheb, which is activated by nutritional uptake, regulate S6K1 and translocation of Rheb is critical for activation of mTOR-S6K1 signaling.