Hyperglycemia and glucose intolerance after mTOR-Is treatment is due to the upregulation of several gluconeogenic genes in the liver via the coordinated activation of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 2 (CRTC2), and forkhead box O1 (FoxO1) (58). Here, CRTC2 is linked to Glucose intolerance.