GCK and Insulin resistance: In addition, expression levels of gluconeogenic genes, phosphoenolpyruvate carboxykinase (Pck1) and glucose 6-phosphatase (G6pc), were up-regulated, whereas the genes involved in glucose utilization, glucokinase (Gck) and hepatic pyruvate kinase (Pklr), were down-regulated in Sphk2-LKO livers (Fig. 3C), which aligned with glucose intolerance and insulin resistance phenotype.