Hypoglycemia and Increased Insulin Sensitivity Following Hypothalamic Lesions. ∗

Abstract

An occasional demonstrable fall in the blood sugar level, in the dog, following traumatic transverse lesions in the hypothalamus at the level of the optic chiasm was observed by us 1 (see 1, Fig. la). Later profound hypoglycemic crises were encountered, also occasionally, when the ventral third or half of the hypothalamus was severed free by a sweeping semicircular cut made with a small blunt instrument 2 (see 2, Fig. la). Subsequently Ingram and Barris described persistent mild hypoglycemia and increased insulin sensitivity following bilateral lesions placed in the region of the paraventricular nuclei in the cat. 3

The question as to the mechanism involved in the precipitation of hypoglycemia, particularly the crises, has attracted our active attention. Below are interpretations drawn from the results obtained thus far in the investigation. The results pertain to experiments on a large series of dogs.

The possibility of the hypothalamic lesions eliminating a normally tonic descending innervation (brainstem) is ruled out on the basis of the following observations: (1) hypoglycemia was precipitated only occasionally by what appeared to be identical lesions; (2) in no instance was hypoglycemia precipitated by lesions that severed the dorso-caudal hypothalamic connections (see 3, Fig. lb); and (3) crises occurred characteristically in the presence of bilateral vagotomy as well as bilateral abdominal sympathectomy.

The possibility of a descending (brainstem) innervation being activated, either by release or by irritative effects of the lesions., - is tentatively ruled out by the failure of vagotomy or sympathectomy to protect against the crises. However, the crucial experiment in this respect has not been carried out, namely, experiments involving both vagotomy and sympathectomy.

The possibility of the hypothalamic lesions eliminating a normally tonic hypothalamico-hypophysial innervation is ruled out on the basis of the failure of hypoglycemia to follow the separation of hypophysis from the hypothalamus by the following procedures, (1) section of the hypophysial stalk at any level, 4 (see 5 and 6, Fig. lb)