Contribution of central and peripheral adrenergic stimulation to IL-1 alpha-mediated glucoregulation.
The present study determined the contribution of central adrenoceptors and the peripheral sympathetic nervous system in regulating the hormonal and glucose metabolic response to intracerebroventricular injection of interleukin (IL)-1 alpha. After an overnight fast, hepatic glucose production (HGP) and peripheral glucose uptake (GU) were assessed in catheterized conscious unrestrained rats using [3-3H]glucose. Intracerebroventricular injection of IL-1 alpha (100 ng) produced a hyperglycemia that resulted from an early increase in HGP (108%) that exceeded a smaller elevation (82%) in GU. Intracerebroventricular injection of the alpha- and beta-adrenergic antagonists phentolamine and propranolol before IL-1 alpha blunted the glucose metabolic response 30-50%. This attenuated response was associated with normalization of the IL-1 alpha-induced hyperglucagonemia and hyperinsulinemia and a 50-60% reduction in the incremental increase in plasma catecholamines. In contrast to central administration, systemic infusion of adrenergic blockers completely prevented the IL-1 alpha-induced increases in plasma glucose, as well as HGP and GU. In these rats, the elevated plasma levels of insulin, glucagon, and corticosterone produced by intracerebroventricular injection of IL-1 alpha were still present. The results indicate that 1) the enhanced whole body glucose metabolism seen after central administration of IL-1 alpha is mediated by increased sympathoadrenal activity and 2) the IL-1 alpha-induced increase in pancreatic insulin and glucagon secretion as well as part of the peripheral catecholamine release is mediated by central adrenoreceptors.
Petit
F
F
Department of Surgery, State University of New York at Stony Brook 11794-8191.
Jarrous
A
A
Dickinson
R D
RD
Molina
P E
PE
Abumrad
N N
NN
Lang
C H
CH
D000315:Adrenalectomy; D000818:Animals; D001921:Brain / Q000502:physiology*; D002395:Catecholamines / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics / Q000008:administration & dosage* / Q000494:pharmacology
D002395:Catecholamines; D006728:Hormones; D007375:Interleukin-1; D013566:Sympathomimetics; D005947:Glucose