INS and Hypoinsulinemia: In vivo evidence supporting insulin and PI3K signaling pathways in the control of DA clearance comes from Patterson et al. [30], who demonstrated that in rats, hypoinsulinemia induced by food deprivation decreases the maximum velocity [Vmax] for DA uptake (with no significant change in the affinity constant [Km] for DA), as determined by rotating disk voltammetry on striatal suspensions.