AICAR

AICAR is an adenosine analog that when phosphorylated forms 5-aminoimidazole-4-carboxamide-1-D-ribofuranosyl-5'-monophosphate (ZMP) which proceeds to activate adenosine monophosphate-activated protein kinase (AMPK). This process in turn stimulates glucose uptake by skeletal muscle in an insulin-dependent manner. Autophagy is initiated by the UNC-51-like kinase 1/2 complex (ULK1 and ULK2). Under basal conditions, autophagy is negatively regulated due to the phosphorylation of ULK1 at serine-757 by mTORC1. During starvation, autophagy is positively regulated by ULK1/2 when it is phosphorylated at serine-555 and serine-777 by AMPK. Therefore, the activation of AMPK by AICAR, in turn will induce autophagy.