AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 6 1918-R1924, Copyright © 1997 by American Physiological Society
Histaminergic contribution to the metabolic effects of neuroglucopenia
P. E. Molina, P. Williams and N. N. Abumrad
Department of Surgery, North Shore University Hospital, Manhasset, New York 11030, USA.
We examined the contribution of central histamine receptor (H1 and H2)
blockade to the glucoregulatory responses to intracerebroventricular
2-deoxy-D-glucose (2-DG) in conscious dogs. Intracerebroventricular 2-DG
(2.5 mg.kg-1.min-1 for 15 min) increased plasma glucose (2-fold), blood
lactate (4-fold), and glycerol (2-fold) levels. The rate of hepatic glucose
production (Ra), determined isotopically, was increased two-fold.
Significant increases over basal were also noted in plasma epinephrine,
norepinephrine, insulin, glucagon, and cortisol. Pretreatment with
cyproheptadine and cimetidine (100 micrograms each icv 15 min before 2-DG)
attenuated the 2-DG-induced hyperglycemia by approximately 50% and delayed
and attenuated the increase in glucose Ra (approximately 85% vs. 2-fold in
group 1). Pretreatment with H1 and H2 antagonists inhibited the increases
in epinephrine, norepinephrine, and glucagon in response to neuroglucopenia
but did not affect the cortisol response. These findings suggest that some
of the metabolic effects of neuroglucopenia, particularly the hyperglycemic
response, the increased hepatic uptake of gluconeogenic precursors, and the
enhanced glucose Ra, are partly mediated through central histaminergic
receptor activation. This appears to be through effects of histaminergic
activation on the autonomic and hormonal responses to central
neuroglucopenia.
