Endotoxin Induced Metabolic Alterations in BCG Infected (Hyperreactive) Mice

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Abstract
The cause of hypoglycemia induced by endotoxin in BCG infected mice was investigated. The major abnormality, known to be defective gluconeogenesis, was studied to determine whether a specific point in the gluconeogenic pathway is involved or whether the derangement is more general. The inability of endotoxin poisoned mice to synthesize glucose from glycerol and fructose in addition to pyruvate indicated that the entire pathway was in disarray. The in vivo oxidation of glucose, glycerol and palmitate to CO2 was reduced, indicating that enhanced aerobic ocidation was not responsible for the hypoglycemia. This decrease in substrate oxidation also suggests that impaired gluconeogenesis may be due to decreased energy available to maintain the gluconeogenic pathway. Pharmacologic doses of glucocorticoids were protective in endotoxin poisoned BCG infected mice. The rate of development of hypoglycemia was rapidly lessened and mortality reduced. Steroids may confer protection by preventing or interfering with some of the toxic effects of endotoxin or perhaps by activating glyconeogenic enzymes. It is unlikely that glucocorticoid mediated enzyme induction plays an anti-endotoxin role in this model.