The molecular mechanism of insul in resistance induced by overnutrition

肝脏在氨基酸摄取和氨基酸合成蛋白质以及一些胰岛素作用中起着关键作用。p70 rebosomal protein kinase 1 （S6K1）是翻译的关键调控因子，其过度激活通过对IRS1的负反馈诱导胰岛素抵抗。然而，其对S6K1的调控作用尚不清楚。在本研究中，我们假设Vps34和Rheb作为营养传感器在mTOR- s6k1信号传导中发挥作用，并且gtp结合的Rheb诱导核内体运输激活mTOR。结果表明，Vps34和通过营养摄取激活的Rheb调控S6K1，而Rheb的易位对mTOR-S6K1信号的激活至关重要。

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.