Effects of toxic and nontoxic endotoxin derivatives on glucose kinetics

Although the polysaccharide portion of bacterial endotoxins (ET) and other components of the bacterial cell wall are known to possess biological activity, the toxic effects produced by ET have been attributed mostly to the lipid-A component. The present study examined the influence of selected gram-negative cell wall components on in vivo carbohydrate homeostasis. Chronically catheterized conscious rats were injected with either ET, lipid A, the White polysaccharide supernatant (WPS-S; polysaccharide-rich and lipid-A-free) or the WPS-precipitate (WPS-P; rich in cell wall components and lipid-A-free) at sublethal doses of 100, 10, and 1 microgram/100 g. The acute hypotensive response to ET and lipid A were similar, while the WPS-P induced a smaller reduction in pressure. Endotoxin, lipid A, or the WPS-P (100 and 10 micrograms) all produced hyperglycemia. Hyperlactacidemia was evident in rats receiving ET, lipid A, and WPS-P; ET-treated animals exhibited the highest lactate concentrations. At the highest doses used, these three fractions increased the rate of glucose appearance. The polysaccharide-rich WPS-supernatant elicited no significant alterations in any of the variables studied. These results indicate that cell wall components of gram-negative bacteria, other than the lipid A of endotoxin, induce changes in carbohydrate metabolism that are similar to those produced by the toxic, lipid-A component of endotoxin.