INS and Hyperglycemia: The actions of insulin on glucose metabolism are mediated by PI3K [14] so it is not surprising that in clinical trials, hyperglycemia was a common effect of many early pan PI3K inhibitors [72,73,74,75,76,77], as well as dual-specificity PI3K/mTOR inhibitors [78] and PI3Kα-specific inhibitors [79,80].