Rapid activation of gluconeogenesis after intracerebroventricular carbachol.
Intracerebroventricular administration of carbachol (27 nmol in 5 microliters 0.15 M NaCl) produced marked hyperglycemia in 24-h fasted rats, despite the negligible amounts of preformed liver glycosyl residues. To investigate the possibility of a stimulation of gluconeogenesis, conscious unrestrained rats were continuously infused with [14C]bicarbonate (0.51 microliters, 0.18 muCi/min) and label incorporation into circulating glucose determined before and after intraventricular injection. The rate of 14C incorporation into blood glucose of fed rats was not affected by intraventricular injection of 0.15 M NaCl but increased significantly after carbachol administration. In both fed and 24-h fasted rats the hyperglycemia induced by intraventricular carbachol was accompanied by marked increases in plasma lactate. Previous adrenodemedullation prevented both the hyperglycemia and the hyperlactemia. Liver pyruvate kinase activity was reduced in carbachol-treated rats, when the enzyme was assayed with suboptimal concentrations of phosphoenolpyruvate and in the absence of fructose 1,6-biphosphate. Phosphoenolpyruvate carboxykinase activity was not affected. The data suggest that central chemical stimulation with cholinergic agents induces a rapid activation of liver gluconeogenesis, which probably results from an increased sympathetic outflow for epinephrine secretion by the adrenal medulla.
Migliorini
R H
RH
Department of Biochemistry, School of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
Garofalo
M A
MA
Roselino
J E
JE
Kettelhut
I C
IC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005215:Fasting; D005943:Gluconeogenesis / Q000187:drug effects*; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism; D007276:Injections, Intraventricular; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D002217:Carbachol