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.
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D004731:Endotoxins / Q000032:analysis*; D005947:Glucose / Q000378:metabolism; D006017:Glycolipids / Q000494:pharmacology*; D007003:Hypoglycemia / Q000139:chemically induced*; D007328:Insulin / Q000494:pharmacology*; D007854:Lead / Q000494:pharmacology; D008050:Lipid A / Q000494:pharmacology*; D008297:Male; D010084:Oxidation-Reduction; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D051381:Rats; D012475:Salmonella; D012477:Salmonella enteritidis
D001786:Blood Glucose; D004731:Endotoxins; D006017:Glycolipids; D007328:Insulin; D008050:Lipid A; D011135:Polysaccharides, Bacterial; D007854:Lead; D005947:Glucose