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.