Proteomics and phosphoproteome analysis revealed a downregulated substrate motif of AKT and hyperactivation of GSK3 in islets of obese diabetic mice, with the latter at least partly contributing to β cell failure.115 Intriguingly, mice carrying mutant GSK3, which blocks phosphorylation by AKT, have higher energy expenditure and are protected from HFD-induced metabolic syndrome.116 Some microRNAs, such as miR-33, miR-143, and miR-153, can inhibit the activity of the PI3K/AKT pathway and induce glucose intolerance in obesity.117. Here, AKT1 is linked to metabolic syndrome.