The role of prostaglandins in endotoxin stimulated glycogenolysis in the liver.

Abstract

Endotoxins or lipopolysaccharides, which are derived from the cell wall of Gram-negative bacteria are thought to cause Gram-negative septic shock. Sepsis leads to an impairment of glucose homeostasis, caused by alterations in hepatic glycogen metabolism. Early endotoxemia generates hyperglycemia, whereas prolonged endotoxemia causes hypoglycemia [I]. Endotoxin in the liver is primarily taken up by Kupffer cells, which are the liver macrophages. Heat-aggregated immunoglobulin which is also taken up by Kupffer cells was shown to stimulate the glucose output in the perfused liver. This effect was found to be mediated by prostaglandins since indomethacin could block the stimulatory effect of heat-aggregated immunoglobulin. Recently we reported that prostaglandins secreted by both Kupffer and endothelial liver cells can stimulate glucose production by parenchymal liver cells [2]. Furthermore we showed that the major prostaglandin of both non-parenchymal liver cell types is PGD 2. In the present work we show that prostaglandins (most probably PGD2) mediate the effect of endotoxin on glucose homeostasis in the liver.