Binding of insulin to its cognate receptor in adipocytes initiates a diverse range of cellular signalling events. These initiating signals rapidly diverge to regulate a multitude of cellular processes including glucose disposal, lipolysis, protein synthesis and transcription. Many of these processes are ultimately regulated via Akt and mTOR which act as key signalling nodes in the cell. Utilizing mass spectrometry-based proteomics we are comprehensively mapping the dynamics of these signals in-vivo in response to acute insulin stimuli. We further dissect the role of the PI3k-Akt pathway using selective inhibitory compounds targeting these nodes. These works highlight the substantial extent to which growth factors such as insulin can modulate intracellular signalling, with over 65% of proteins containing phosphorylation sites (most proteins containing multiple sites), and almost 20% of these sites significantly responding. Using advanced bioinformatics approaches we identify and classify unique components of the signalling network, and identify many new substrates regulated in response to insulin. These data identify a diverse range of cellular functions regulated by insulin and emphasise the enormous potential of mass spectrometry-based proteomics for the study of signalling.