In vivo studies were undertaken in rats to provide evidence for the neural nature, tentative localization and mode of excitation of the insulin-sensitive central nervous system (CNS) glucoregulator center.

In rats under light barbiturate anesthesia minute amounts of insulin injected into the carotid artery resulted in an immediate decrease of the systemic blood sugar. This hypoglycemic action of regional insulinization of the CNS was lost when the animals were subjected to prolonged, deep barbiturate narcosis.

Competitive inhibition of glucose utilization in the CNS region by intracarotid administration of 2-deoxy-D-glucose did not block the systemic hypoglycemic effect of subsequent intracarotid insulin injection. Chronic endogenous hyperinsulinemia produced by daily growth hormone treatment resulted in an insensitivity of the CNS glucoregulator center to exogenous insulin. The ratio of the quantity of the injected insulin and the pre-existent plasma insulin concentration showed direct correlation with the systemic hypoglycemic response that followed intracarotid injection.

Present data support the hypothesis that the insulin-sensitive glucoregulator center located in the area supplied by the carotid artery is neural in nature, because of its inhibition by barbiturate anesthesia. The data are compatible with the working hypothesis that the center is located in the hypothalamus, since light cortical barbiturate anesthesia did not, but deep anesthesia did have an inhibitory effect on it.

Marked interference by chronic hyperinsulinemia suggests that the receptor center estimates the metabolic status of the animal through means related to physicochemical binding of insulin to specific receptors. However, since our attempt to inhibit glucose utilization in the CNS was without effect on the activity of the center, it appears that the signal for the glucoregulatory impulse is not insulin facilitation of glucose utilization in the receptor area, but another parameter of insulin action.