INS and Insulin resistance: Taken together, the above mechanisms provide a comprehensive explanation for the observation that inhibition of PI3K–AKT–mTOR pathway can lead to abrogated insulin function, impaired insulin secretion and development of insulin resistance (Crouthamel et al, 2009; Houde et al, 2010; Lamming et al, 2012; Fang et al, 2013).