This application proposes a continuation of my neurobavioral analysis of glucagon's role in the control of postprandial satiety. The effects of glucagon on spontaneous meals will be investigated in free-feeding rats in order to characterize further the contexts in which it controls meal size, to elucidate its neuroendocrine mechanisms, and to establish its role in the regulation of body weight. The project's general goal is to advance understanding of the physiolo- gical controls of feeding. This is a central problem in the physiological psychology of motivation. Its solution is also prerequisite for the development of physiologically-based treatments of clinical disorders such as obesity, bulimia, and anorexia nervosa. These investigations are especially relevant in the view of the evidence that physiologic glucagon doses inhibit appetite in humans and that endogenous glucagon is necessary for the normal control of spontaneous meals in rats. The proposed experiments measure feeding in undisturbed free-feeding rats administered meal-contingent hepatic portal glucagon infusions. Both infusions and data collection are computer-controlled.
The specific aims of the project are to determine: (1) The infusion parameters maximizing glucagon's satiety effect. (2) Whether the liver is the site of glucagon's satiety effect. (3) Whether stimulation of fatty acid oxidation causes the satiety effects of exogenous and endogenous glucagon. (4) Whether prandial hepatic glycemic changes contribute to glucagon satiety. (5) The role of insulin-dependent glucose utilization in glucagon satiety. (6) Glucagon's effect in rats that are offered food choices. (7) The dose-response relation of the stimulatory effect on feeding of antagonism of endogenous glucagon by glucagon antibody infusion. (8) The effects of repeated meal-contingent glucagon infusions on food intake and body weight.
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