Investigating the Effects of Lithium and AKT Inhibitors on Insulin Resistance in a Rat Model

Insulin resistance, a fundamental aspect of metabolic diseases like type 2 diabetes and obesity, is defined by compromised insulin signaling and glucose absorption. This study sought to examine the impact of lithium, Protein Kinase B (PKB) or AKT inhibitors, and their combination on insulin resistance in a rat model generated by a high-fat diet (HFD). Fifty male albino rats were categorized into five groups: a control group, a high-fat diet (HFD) group, and three HFD treatment groups administered lithium, AKT inhibitors, or a combination thereof. Over a four-week period, we evaluated fasting insulin, blood glucose, HOMA-IR, liver function markers (Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)), triglycerides (TG), inflammatory markers (Interleukin-1 beta (IL-1β), Tumor Necrosis Factor-alpha (TNF-α)), oxidative stress parameters (Malondialdehyde (MDA), Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Catalase (CAT)), and gene expression associated with insulin signaling (insulin receptor (IR), Akt, glucose transporter type 4 (GLUT 4)). The findings indicated that both lithium and AKT inhibitors markedly enhanced metabolic, hepatic function, and inflammatory indicators. The AKT inhibitor alone was most efficacious in diminishing lipid peroxidation and inflammation, but the combined therapy offered the most comprehensive antioxidant protection. The data indicate that lithium and AKT inhibitors, either individually or in conjunction, may have therapeutic functions in the treatment of insulin resistance and metabolic diseases.