There is universal agreement that only a fraction of the amount consumed during a meal is absorbed from the digestive system before the meal is terminated and that peripheral sensory systems, therefore, play a critical role in short-term satiety and in the control of meal size. However, considerable controversy surrounds the issue of the identity and location of the peripheral receptors from which satiety-relevant feedback originates. the debate is marked by the advocacy of single-organ models of satiety (e.g., """"""""the stomach signals satiety"""""""") despite good evidence that receptors at several locations can provide complementary or redundant information about what has been ingested during the meal (volume, nutrient content, calories, etc.). As a result, almost no data speak to the integration of intake-inhibitory signals when feedback from oral, gastric and post-gastric sources are concurrently available. This is a serious omission for clinical approaches to feeding disorders and for neural investigations into substrates that modulate ingestive behavior as a function of physiological and metabolic variables. Experiments proposed will address these issues. The present experiments will provide a systematic analysis, in the rat, of the relative contributions of oral, gastric and post-gastric signals to terminating bouts of glucose ingestion initiated under controlled laboratory conditions. to determine the gastric versus post-gastric distribution of ingested glucose, measurement of the cumulative intake curve will be coordinated with what will be the first systematic measurements of gastric emptying during ingestion. It will thereby be possible to quantify the stimulatory effects of experimental manipulations (stimulus concentration, stimulus delivery rate, gastric infusions of glucose delivered at different rates in parallel with oral ingestion) designed to systematically bias the rate of glucose accumulation within the stomach relative to the rate at which glucose empties from the stomach. Their behavior impact will be evaluated in terms of (1) changes in meal size and meal duration, and (2) the amount of glucose within and beyond the stomach when meals are terminated. these experiments will lead to the identification of peripheral sources of satiety-relevant feedback and to an operational model for the integrative mechanisms that underlie short-term satiety under normal conditions when oral, gastric and postgastric receptors are stimulated concurrently.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK042284-01A1
Application #
3243327
Study Section
Biopsychology Study Section (BPO)
Project Start
1993-01-01
Project End
1995-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Faulconbridge, Lucy F; Grill, Harvey J; Kaplan, Joel M et al. (2008) Caudal brainstem delivery of ghrelin induces fos expression in the nucleus of the solitary tract, but not in the arcuate or paraventricular nuclei of the hypothalamus. Brain Res 1218:151-7
Williams, D L; Grill, H J; Cummings, D E et al. (2006) Overfeeding-induced weight gain suppresses plasma ghrelin levels in rats. J Endocrinol Invest 29:863-8
Faulconbridge, Lucy F; Grill, Harvey J; Kaplan, Joel M (2005) Distinct forebrain and caudal brainstem contributions to the neuropeptide Y mediation of ghrelin hyperphagia. Diabetes 54:1985-93
Grill, Harvey J; Carmody, Jill S; Amanda Sadacca, L et al. (2004) Attenuation of lipopolysaccharide anorexia by antagonism of caudal brain stem but not forebrain GLP-1-R. Am J Physiol Regul Integr Comp Physiol 287:R1190-3
Daniels, Derek; Markison, Stacy; Grill, Harvey J et al. (2004) Central structures necessary and sufficient for ingestive and glycemic responses to Urocortin I administration. J Neurosci 24:11457-62
Williams, Diana L; Cummings, David E; Grill, Harvey J et al. (2003) Meal-related ghrelin suppression requires postgastric feedback. Endocrinology 144:2765-7
Faulconbridge, Lucy F; Cummings, David E; Kaplan, Joel M et al. (2003) Hyperphagic effects of brainstem ghrelin administration. Diabetes 52:2260-5
Williams, Diana L; Grill, Harvey J; Cummings, David E et al. (2003) Vagotomy dissociates short- and long-term controls of circulating ghrelin. Endocrinology 144:5184-7
Williams, D L; Bowers, R R; Bartness, T J et al. (2003) Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat. Endocrinology 144:4692-7
Grill, Harvey J; Schwartz, Michael W; Kaplan, Joel M et al. (2002) Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology 143:239-46

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