At pathological concentrations (50 μM), TMAO was found to bind and activate PERK both in vitro and in vivo, which in turn, induced FoxO1 and thereby upregulates the gluconeogenic genes G6pc (glucose-6-phosphatases), pck1 (cytosolic phosphoenolpyruvate carboxykinase) in the liver, leading to hyperglycemia. This evidence concerns the gene PCK1 and Hyperglycemia.