Moreover, since HMW-adiponectin/T-cadherin system is responsible for ceramide removal from the cell [97], any dysfunction in the system can further aggravate impaired signaling, including the insulin resistance. In such circumstances metformin, acting on adiponectin pathway and inducing AMPK activation downstream of adiponectin receptors, can be a therapy of choice [233]. This evidence concerns the gene ADIPOQ and Insulin resistance.