Insulin plays a key role in the maintenance of normal glucose tolerance by suppressing endogenous glucose production during a meal. Insulin is not, however, involved in the regulation of splanchnic glucose uptake. The latter process appears, based on studies performed in dogs, to be regulated primarily by the arterial-portal glucose gradient and to a smaller extent by glucose mass-action. Regarding peripheral glucose utilization, insulin is not needed to maintain a normal rate of glucose utilization since this can also be achieved by hyperglycaemia and glucose mass-action. Insulin is, however, necessary for the maintenance of normal rates of glucose oxidation and storage in insulin-sensitive tissues, and for the prevention of excessive gluconeogenic substrate production.