AKT1 and Insulin resistance: Some SIRT-1 activators, such as JHJ1, JHJ2, and JHJ3 (derived from the structure of OAP) [82], have been reported to modulate the plasma lipid metabolism and blood glucose in high-fat fed mice by upregulating FoxO1, PPARγ, and PGC-1α genes [83], while another activator, named E6155 (identified by a high-throughput screening using the purified recombinant human SIRT-1 and HTRF SIRT-1 assay) by Liu and colleagues, improved blood glucose tolerance and insulin resistance in diabetic mice by activating LKB1/AMPK and IRS1/AKT pathways [84].