Endotoxin and tryptophan-induced hypoglycaemia in rats.
Pretreatment of rats with increasing, but non-lethal, doses of endotoxin was associated with a parallel increase in sensitivity to induction of hypoglycaemia by tryptophan. Acutely streptozotocin-diabetic animals became hypoglycaemic with endotoxin alone, and this was increased further by tryptophan. Variations in tryptophan sensitivity between rat populations cannot be explained by previous history of exposure to endotoxin. Endotoxin abolished the increase in tryptophan dioxygenase activity caused by triamcinolone, but not that caused by tryptophan. Triamcinolone was effective, however, when given together with tryptophan to endotoxin-treated rats. The activity of tryptophan dioxygenase in vivo and in liver cells in vitro is unchanged by exposure to endotoxin at 1 mg/kg body wt. Turnover studies indicated that hypoglycaemia resulted from inhibition of gluconeogenesis. There was no evidence to support a role for insulin in this process and results were consistent with an endotoxin-mediated hepatic insensitivity to glucagon. They also suggested that quinolinate, rather than 5-hydroxytryptamine, may be the intracellular agent responsible for inhibition of gluconeogenesis.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D007003:Hypoglycemia / Q000139:chemically induced*; D051381:Rats; D012701:Serotonin / Q000502:physiology; D013217:Starvation / Q000378:metabolism; D014221:Triamcinolone / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D001786:Blood Glucose; D004731:Endotoxins; D014221:Triamcinolone; D012701:Serotonin; D014364:Tryptophan; D014366:Tryptophan Oxygenase