Central administration of interleukin 1 elicits hyperinsulinemia in rats.
This laboratory previously demonstrated that human natural interleukin 1 (IL-1) administered intravenously at a dose of 50 U to conscious fasted male Holtzman rats elicited unstimulated as well as glucose- and arginine-stimulated hyperinsulinemia. The major question posed in the present investigation is whether the monokine IL-1 can act centrally on an area of the brain such as the preoptic area of the anterior hypothalamus, which participates in mediating the IL-1-induced febrile response, to elicit insulin secretion by the pancreas. Therefore, for this study, injections of IL-1 were administered intravenously (iv), intracerebroventricularly (icv), or into the preoptic area of the anterior hypothalamus (iPO) in pentobarbital-anesthetized fasted rats. Preliminary experiments determined that the hyperinsulinemic response was enhanced in anesthetized compared with conscious animals treated iv with IL-1. An icv administered 10-U dose of the monokine produced a delayed hyperinsulinemia equal to two times the saline control value starting near 20 min postinjection but declining quickly. When injected iPO, 5 U of IL-1 elicited a prompt substantial hyperinsulinemia equal to more than three times control beginning at 5 min postinjection and persisting through the 30-min experimental period. These findings indicate that an IL-1-induced signal for pancreatic insulin secretion can be generated within the central nervous system.
Cornell
R P
RP
Division of Science, Northeast Missouri State University, Kirksville 63501.
Schwartz
D B
DB
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006946:Hyperinsulinism / Q000139:chemically induced*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000008:administration & dosage / Q000633:toxicity*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012016:Reference Values
D007328:Insulin; D007375:Interleukin-1; D001120:Arginine; D005947:Glucose