Interleukin 1: a regulatory role in glucocorticoid-regulated hepatic metabolism.
The purpose of this study was to investigate the effect of interleukin 1 (IL 1) on glucocorticoid-regulated hepatic metabolism. Steroid binding in liver cytosol, plasma glucose, plasma corticosterone, and phosphoenolpyruvate carboxykinase (PEPCK) activity were assayed in C3H/HeJ mice after IL 1 administration. Mice received 5 pyrogenic U (PU) of rabbit IL 1 i.p. and were sacrificed 4 hr later. In adrenal-intact mice, steroid binding and plasma glucose were significantly decreased (63 and 64% of control) and plasma corticosterone was significantly elevated threefold. In adrenalectomized mice, IL 1 (5 PU) treatment produced similar results in steroid binding (66% of control) and plasma glucose (71% of control). PEPCK was measured in intact mice fasted overnight and treated with 5 PU of IL 1. PEPCK was induced in fasted control animals (23.1 +/- 1.4 U/mg) vs fed control animals (15.9 +/- 0.7 U/mg). IL 1 treatment inhibited the induction of PEPCK in fasted animals (13.4 +/- 2.0 U/mg) and caused a significant decrease in steroid binding (78% of fasted control) and plasma glucose (82% of fasted control). No difference in plasma corticosterone was seen in IL 1-treated mice and fasted control mice. These data indicate that IL 1 decreases intracellular steroid receptors, resulting in decreased induction of PEPCK and subsequent reduced gluconeogenesis and plasma glucose. We propose that IL 1 plays a regulatory role in glucocorticoid-regulated hepatic metabolism.
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D007375:Interleukin-1 / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000187:drug effects
D001786:Blood Glucose; D007375:Interleukin-1; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D003345:Corticosterone