Lack of understanding of the physiological bases of eating impedes progress in resolving the difficult health problems posed by eating disorders.

In 1982, Dr. Geary and his colleagues provided evidence that prandial glucagon secretion initiates a signal that is necessary for the normal termination of meals in rats. Further work indicated that the signal initiated by glucagon originates in the liver and is probably relayed to the brain via vagus nerve. In a recent double-blind study conducted in normal-weight men, intravenous glucagon infusions during meals reduced appetite and meal size without producing any side effects. Current work concerns how glucagon's satiety effect is mediated. One set of experiments investigates the relationship of glucagon's satiating effect to its metabolic actions and the actions of pancreatic insulin and amylin. Additionally, the possibility that glucagon acts directly on hepatic vagal afferent fibers is being pursued using autoradiographic assays for glucagon in the vagus nerve.

Another of Dr. Geary's research programs concerns how the ovarian hormone estradiol modulates feeding. In female rats, a decrease in meal size follows the pre-estrus increase in circulating estradiol, and ovariectomy causes a chronic increase in meal size and body weight that can be reversed by estradiol replacement. Ongoing experiments have demonstrated that increases in the satiating action of the gut peptide cholecystokinin mediate a substantial part of estradiol's inhibitory action on feeding. The site of such interactions and their physiological mechanisms are the subject of current work. This project's rationale is that understanding the physiological interactions of estradiol with peripheral controls of meal size in rats may provide useful models for effect of estradiol on appetite and food intake in women.