Involvement of endogenous opiates in glucose-stimulated hyperinsulinism of canine endotoxin shock. Inhibition by naloxone.
Hyperinsulinism has been associated with infection and endotoxin shock in rodents, dogs, and humans. In dogs with Escherichia coli-induced endotoxin shock, this hyperinsulinism was in response to glucose administration. To determine the role of endogenous opiates in endotoxin-induced glucose-stimulated hyperinsulinism, plasma beta-endorphin, Met-enkephalin, Leu-enkephalin, insulin, and glucose concentrations were measured for 6 h in fasted, anesthetized dogs given LD70 of E. coli endotoxin; endotoxin and glucose; endotoxin, glucose, and naloxone (an opiate antagonist); glucose and naloxone; or glucose alone. Plasma endogenous opiate immunoreactivity was elevated in dogs that received endotoxin, regardless of the presence of glucose or naloxone. The elevation of plasma Met-enkephalin and beta-endorphin preceded the onset of hyperinsulinism, but the elevation of plasma Leu-enkephalin did not. Plasma insulin was elevated 100-fold by 360 min in dogs given endotoxin and glucose. The magnitude of this hyperinsulinism was markedly reduced by naloxone, supporting the hypothesis that endogenous opiates are involved in the development of the glucose-stimulated hyperinsulinism associated with endotoxin shock. Interestingly, naloxone, given in conjunction with glucose, appeared to have a stimulatory effect on insulin secretion.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D004723:Endorphins / Q000097:blood / Q000502:physiology*; D004731:Endotoxins; D004743:Enkephalin, Leucine / Q000097:blood; D004744:Enkephalin, Methionine / Q000097:blood; D004926:Escherichia coli; D005947:Glucose / Q000494:pharmacology*; D006946:Hyperinsulinism / Q000097:blood / Q000209:etiology*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D012772:Shock, Septic / Q000097:blood / Q000150:complications*; D001615:beta-Endorphin
D001786:Blood Glucose; D004723:Endorphins; D004731:Endotoxins; D007328:Insulin; D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D005947:Glucose