Change in sensitivity to insulin hypoglycemic convulsions after gold thioglucose treatment: time course of development

JL Luby, JF Holliday, KW Fish and MA Marrazzi

The sensitivity to insulin hypoglycemic convulsions has been shown to decrease at early times (16 and 24 hr) and increase at later times (1 week) after gold thioglucose (GTG) treatment. Systemically administered GTG is well known to produce hyperphagia, resulting in obesity, and cytological damage focused relatively selectively in the ventromedial hypothalamic area (VMH). Both of these effects on insulin hypoglycemic convulsions occur before the weight gain, but at a time when histological damage visible with cresyl violet stain has already appeared. Both of these changes reflect a difference in the convulsive response to hypoglycemia, rather than a differences in the degree of hypoglycemia in response to insulin. No functional change in the convulsive sensitivity was found at still earlier times during the latency in establishing the histological damage visible with cresyl violet. These results suggest that GTG lesions a relatively discrete brain region involved in adjusting the functional response of the brain to hypoglycemia, including a composite of two opposite regulatory components. The significance of such a control center in relation to energy metabolism in brain is discussed. Moreover, it has been postulated that the glucose moiety of GTG binds to glucoreceptors in the VMH to focus the cytoxicity of the gold thioportion at that site. These results are also discussed in relation to this proposed mechanism for concentration and hence localization of GTG toxicity in the VMH.

Volume 219, Issue 1, pp. 258-267, 10/01/1981
Copyright © 1981 by American Society for Pharmacology and Experimental Therapeutics