AMPK Activation Suppresses mTOR/S6K1 Phosphorylation and Induces Leucine Resistance in Rats with Sepsis.

This study aimed to investigate the AMPK/mTOR pathway in sepsis-induced leucine resistance and its upstream signals, and to seek a way to correct leucine resistance in sepsis. Sepsis was produced by cecal ligation and puncture (CLP) model in rat. Both septic rats and sham operation rat received TPN with or without leucine for 24 hours, and then protein synthesis and AMPK/mTOR and PKB were tested. In vitro C2C12 cells were treated with or without leucine, and we tested the AMPK/mTOR pathway and protein synthesis. We blocked AMPK by compound C and stimulated it by AICAR individually. The results showed that AMPK was highly phosphorylated and suppressed mTOR/S6K1 activation in CLP rats. In vitro when AMPK was activated by AICAR, protein synthesis was suppressed and leucine resistance was observed. High phosphorylation of AMPK was accompanied by PKB inactivation in CLP rats. When PKB was blocked, both AMPK activation and leucine resistance were observed. In CLP rats, nutrition support with intensive insulin therapy reversed leucine resistance by activating PKB and suppressing AMPK phosphorylation. These findings suggest that high phosphorylation of AMPK induced by PKB inactivation in sepsis suppresses mTOR, S6K1 phosphorylation and protein synthesis, and leads to leucine resistance. Intensive insulin treatment can reverse leucine resistance by suppressing AMPK activation through activation of PKB. This article is protected by copyright. All rights reserved. PMID: 31943518...
Source: Cell Biology International - Category: Cytology Authors: Tags: Cell Biol Int Source Type: research