Relation of endotoxin structure to hypoglycemic and insulinlike actions

Various endotoxin preparations were used to determine which portion of endotoxin, lipid A, polysaccharide, or lipid-associated protein (LAP), mediates the hypoglycemic and insulinlike action in rats. Salmonella enteriditis Boivin (SEB), complete endotoxin, and S enteriditis Westphal (SEW), lacking LAP, were equally lethal to endotoxin-sensitized rats; however, S minnesota (SM) glycolipid (lipid A plus 16% polysaccharide) was comparatively more toxic. Toxic effects were prevented by alteration of lipid A through alkaline hydrolysis or polymixin B treatment. SM-lipid A (0.02% polysaccharide) was less toxic than SM-glycolipid. Similar hypoglycemic effects were produced by SEB and SEW; however, SM-glycolipid produced a significantly greater hypoglycemia. Although SEB, SEW, and SM-glycolipid all produced significant increases in adipose tissue glucose oxidation a decreasing trend in effectiveness was observed, while the SM-lipid A was without effect. However, adding detoxified hydrolysates of endotoxin to SM-lipid A produced a significant increase in glucose oxidation. In conclusion, lipid A is the primary endotoxin moiety mediating both the lethal effects of endotoxin and its hypoglycemic action. However, maximal expression of insulinlike action requires the presence of all three portions of endotoxin.