The term insulin dysregulation encompasses different disturbances of insulin regulation in equids, including basal or a pathological high postprandial hyperinsulinemia and/or peripheral insulin resistance. Alterations of insulin signaling, as seen in human type II diabetes mellitus, might be associated with the development of insulin dysregulation, but the underlying pathomechanisms have not been elucidated yet. Therefore, the objective of this study was to determine key proteins of the insulin signaling cascade in insulin dysregulated and healthy horses under basal conditions and after an oral glucose and intravenous insulin challenge. Secondly, the insulin and glucose response to an IV insulin and oral glucose challenge was described to assess glucose and insulin dynamics following different challenges. In principle, insulin signaling was maintained, but the signaling cascade was modified, especially at post-receptor events, in relation to the source of insulin. Thus, ID seems to be an equine-specific metabolic condition, in which alterations of the mTOR signaling pathway may play a crucial role, emphasized by higher mTOR phosphorylation in ID horses. Furthermore, the results of the study support that both terms, hyperinsulinemia and insulin resistance, have to be clearly distinguished in the context of insulin dysregulation.