AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 1 116-R122, Copyright © 1993 by American Physiological Society
Glucagon acts in the liver to control spontaneous meal size in rats
N. Geary, J. Le Sauter and U. Noh
Department of Psychiatry, Cornell University Medical College, White Plains, New York.
To determine the site of origin of pancreatic glucagon's inhibitory effect
on spontaneous feeding in rats, glucagon was infused into either the
hepatic portal vein or the inferior vena cava during spontaneous meals late
in the dark phase. Hepatic portal infusion of 1.7-13.6 micrograms
glucagon/meal reduced spontaneous meal size. In contrast, these doses did
not significantly affect meal size when delivered via vena caval catheters
that ended near the junction of the hepatic vein. This difference indicates
that glucagon receptor sites in the liver initiate the satiating action of
glucagon during spontaneous meals. The vagal dependency of glucagon satiety
was also tested. Hepatic portal infusion of 13.6 micrograms glucagon/meal
reduced the size of spontaneous meals both early and late in the dark in
neurally intact rats, but not in hepatic-vagotomized rats. Finally,
antagonism of endogenous glucagon with hepatic portal infusion of glucagon
antibodies in a dose sufficient to neutralize 1 ng glucagon in vitro
increased spontaneous meal size in intact rats, but not in
hepatic-vagotomized rats. Thus the satiating effects of both exogenous and
endogenous glucagon on spontaneous food intake appear to depend on the
hepatic branch of the vagus. Taken together, these results are consistent
with the hypothesis that glucagon acts in the liver to produce a satiety
signal that is transmitted to the brain by the hepatic branch of the
abdominal vagus.
