Abstract

This application proposes a continuation of my neurobehavioral analysis of glucagon's role in the control of postprandial satiety in the rat. The planned experiments are designed to compare the inhibitory controls of meal size exerted by endogenous and by exogenous glucagon, to characterize further the contexts in which exogenous glucagon controls meal size, to elucidate the physiological and neural mechanism mediating glucagon's satiety effect, and to investigate the interactions between exogenous glucagon and other hypothesized satiety signals. The general goal of the project is to advance understanding of the physiological controls of feeding behavior. This is a major problem in behavioral neuroscience whose solution is a prerequisite for the development of physiologically-based treatments of clinical disorders such as obesity, bulimia, and anorexia nervosa. The investigation of the satiety effect of exogenous glucagon is especially relevant in this context because there is evidence that endogenous glucagon is necessary for the normal control of meal size in the rat.
The specific aims of the project are: (1) Use glucagon antibody injections to establish the relation between the satiety effects of exogenous and endogenous glucagon. (2) Pharmacologically antagonize free fatty acid oxidation to determine whether free fatty acid oxidation may play a causal role in exogenous glucagon's satiety effect. (3) Perform peripheral neural lesions to determine the abdominal innervation necessary for the synergistic satiety effect of glucagon and cholecystokinin on sham feeding in rats with gastric cannulas. (4) Determine whether glucagon synergizes with intraduodenal nutrient infusions to elicit satiety in sham feeding rats and investigate whether endogenous cholecystokinin might mediate such an effect. (5) Determine whether different peripheral neural mechanisms mediate the satiety effects of glucagon at different circadian times. (6) Investigate whether exogenous glucagon synergizes with exogenous somatostatin or exogenous insulin to elicit satiety.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK032448-08
Application #
3230842
Study Section
Biopsychology Study Section (BPO)
Project Start
1982-09-01
Project End
1991-05-31
Budget Start
1989-07-01
Budget End
1991-05-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
Graduate Schools
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027

  Publications

Geary, N; Asarian, L (2001) Estradiol increases glucagon's satiating potency in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol 281:R1290-4
Geary, N (1999) Effects of glucagon, insulin, amylin and CGRP on feeding. Neuropeptides 33:400-5
Geary, N (1996) Failure of pulsatile infusion to increase glucagon's satiating potency. Physiol Behav 59:613-6
Surina-Baumgartner, D M; Langhans, W; Geary, N (1995) Hepatic portal insulin antibody infusion increases, but insulin does not alter, spontaneous meal size in rats. Am J Physiol 269:R978-82
Geary, N; Trace, D; Smith, G P (1995) Estradiol interacts with gastric or postgastric food stimuli to decrease sucrose ingestion in ovariectomized rats. Physiol Behav 57:155-8
Geary, N; Trace, D; McEwen, B et al. (1994) Cyclic estradiol replacement increases the satiety effect of CCK-8 in ovariectomized rats. Physiol Behav 56:281-9
Le Sauter, J; Geary, N (1993) [Pancreatic glucagon: physiological signal of postprandial satiety] Ann Endocrinol (Paris) 54:149-61
Geary, N; Le Sauter, J; Noh, U (1993) Glucagon acts in the liver to control spontaneous meal size in rats. Am J Physiol 264:R116-22
Geary, N; Fudge, J; Le Sauter, J (1992) Scheduled running wheel activity indexes the specificity of pharmacological anorexia. Behav Neural Biol 58:1-7
Geary, N; Kissileff, H R; Pi-Sunyer, F X et al. (1992) Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men. Am J Physiol 262:R975-80

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