Effects of Gold Thioglucose on 2-Deoxyglucose Hypoglycemic Convulsions
Ryan, Daniel M.
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Insulin hypoqlycemia, fluoroacetate 2-deoxyglucose (2DG) all induce· metabolic convulsions, presumably due to a fuel shortage. Insulin hypoglycemia decreases overall glucose metabolism by decreasing the glucose available to brain. Fluoroacetate blocks the Krebs cycle, by being converted to fluorocitrate which blocks the citrate to isocitrate step. 2DG blocks glycolysis after the hexokinase step. These three metabolic convulsants can be qualitatively differentiated on the basis of the effects of gold thioqlucose (GTG) and 5-thioqlucose (5TG) in female CBA/J mice. A single IP injection of GTG causes a cytotoxic lesion focused in the ventromedialarcuate hypothalamus (VMH) and a biphasic change in the sensitivity to insulin hypoglycemic convulsions. The percentage of mice convulsing in a population is decreased at early times (16-24 hours) and increased at later times (1-2 weeks> after GTG. Blood glucose measurements indicated that both changes are differences in the convulsive response to equal hypoglycemia, rather than the hypoglycemic response to insulin. 5TG simulates the early component of the GTG effect on insulin hypoglycemic convulsions (without causing lesions), but has no effect at one week. GTG lesions did not alter the sensitivity to the metabolic convulsant fluoroacetate or to the metabolic convulsant 2-deoxyqlucose. Thus, although related in both cases to a shortage of available cellular fuel, the metabolic convulsions induced by insulin hypoglycemia and by those of fluroacetate and 2DG must be qualitatively different. The regulatory mechanism lesioned by gold thioglucose, the "gold thioglucose iesioned glucostat", did not appear to require the blockage of metabolism at the sites blocked by fluoroacetate or 2-Deoxyglucose.