Endogenous gut-derived bacterial endotoxin tonically primes pancreatic secretion of insulin in normal rats.
This laboratory has proposed that endogenous gut-derived bacterial endotoxin primes the pancreatic secretion of insulin in normal rats. Endogenous lipopolysaccharide (LPS) is continually absorbed from the gut into intestinal capillaries, and low-grade portal venous endotoxemia is the status quo. Under physiologic conditions, Kupffer cells of the liver totally phagocytize and degrade endotoxin from the portal circulation. Evidence from this and other laboratories indicates that administration of exogenous LPS to humans and rats enhances pancreatic secretion of both insulin and glucagon. Conversely, findings of the present study demonstrate that restriction of endogenous LPS in fasted rats depresses the basal and arginine-stimulated concentrations of plasma insulin. Techniques used to restrict gut-derived LPS availability included chronic daily gavage with neomycin and cefazolin for gut sterilization and with cholestyramine or lactulose to reduce endotoxin within the gut. In addition, induction of endotoxin tolerance was produced by progressively higher doses of LPS intraperitoneally (i.p.), and polymyxin B was administered subcutaneously (s.c.) daily to neutralize the lipid A portion of circulating LPS. Finally, isolator-reared, defined flora rats, which were gram-negative-bacteria-deficient, and, therefore, LPS-deficient, were compared with conventional counterparts. Basal plasma insulin but not glucagon levels were consistently and significantly reduced in endogenous LPS-restricted animals. Glucose-stimulated plasma insulin was decreased only after parenteral treatment by tolerance induction and polymyxin B administration. Both plasma insulin and glucagon were depressed in response to arginine challenge in most LPS-restricted rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D004064:Digestive System / Q000382:microbiology; D004731:Endotoxins / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D051381:Rats; D012477:Salmonella enteritidis
D001786:Blood Glucose; D004731:Endotoxins; D007328:Insulin; D005934:Glucagon; D001120:Arginine; D009355:Neomycin