AJP - Endocrinology and Metabolism, Vol 257, Issue 4 E486-E490, Copyright © 1989 by American Physiological Society
Rapid activation of gluconeogenesis after intracerebroventricular carbachol
R. H. Migliorini, M. A. Garofalo, J. E. Roselino and I. C. Kettelhut
Department of Biochemistry, School of Medicine, University of Sao Paulo, Ribeirao Preto, Brazil.
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.
