Histaminergic contribution to the metabolic effects of neuroglucopenia.
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.
Molina
P E
PE
Department of Surgery, North Shore University Hospital, Manhasset, New York 11030, USA.
Williams
P
P
Abumrad
N N
NN
D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood; D003847:Deoxyglucose / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000172:deficiency*; D005990:Glycerol / Q000097:blood; D006632:Histamine / Q000502:physiology*; D006728:Hormones / Q000097:blood; D007276:Injections, Intraventricular; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male
D001786:Blood Glucose; D002395:Catecholamines; D006728:Hormones; D019344:Lactic Acid; D006632:Histamine; D003847:Deoxyglucose; D005947:Glucose; D000409:Alanine; D005990:Glycerol