LPS produces a transient hyperglycemia which results, in part, from an elevation in the rate of hepatic glucose production (HGP). Previous studies have demonstrated that LPS also increases IL-1 within the brain, and that the intracerebroventricular (ICV) injection of IL-1 stimulates HGP in control rats. The purpose of the present study was to determine whether the enhanced production of IL-1 within the brain mediates the LPS-induced increase in glucose flux. To accomplish this goal, a specific receptor antagonist for IL-1 (IL-1ra; Amgen) or saline was infused ICV prior to and for 4 h after the intravenous (IV) injection of LPS. Whole body glucose flux was measured in conscious unrestrained rats using [33Hlglucose. Injection of LPS increased both the plasma glucose concentration and HGP (78% and 85%, respectively). In contrast, ICV infusion of the IL-1ra (2 g/kg + 2 mg/kg/h) attenuated the LPS-induced changes in glucose metabolism by more than 50%. An IV infusion of the same dose of IL-1ra, however, did not blunt the LPS-induced increase in glucose flux. ICV injection of IL-Ira also attenuated the LPS-induced hyperlactacidemia, but did not alter the increase in muscle pyruvate dehydrogenase activity. These data indicate that a major portion of the increase in glucose and lactate concentrations as well as the stimulation of HGP produced by LPS is mediated by IL-1 within the central nervous system. (Supported by NIH GM 38032, GM 50919 and GM 39277).
|Original language||English (US)|
|State||Published - 1996|
All Science Journal Classification (ASJC) codes
- Molecular Biology