The control of food intake and adiposity by mammals is complex and includes contributions from many factors. We are particularly interested in the role of peptide hormones in this control system. One category of these hormones, called satiety factors or hormones, are secreted from the gut in response to a meal. As they accumulate in the blood (or some critical organ), they eventually cause the person or animal to stop eating. Another category of these hormones includes those (especially insulin) which is secreted in proportion to adiposity. As one gains weight, this signal increases and ultimately causes decreased food intake by acting at the bran; conversely, if one loses weight, the signal diminishes and appetite (food intake) is increased. We believe that insulin is this signal and that it gains access to critical brain areas via the cerebrospinal fluid (CSF). We propose to investigate the relationships among plasma and CSF insulin, and food intake and body weight in rats. We use genetically obese Zucker rats because we have evidence that their obesity may be due to a defect in the brain-insulin system. We also use rats with hypothalamic and dietary obesity, as well as diabetic rats. We propose to change the amount of insulin in the CSF and in the blood and determine the effects upon food intake and body weight. Satiety hormones we investigate include cholecystokinin (CCK) and bombesin (BBS). Besides investigating further their physiology, we shall determine how the insulin-adiposity system interacts with the satiety system to control body weight.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM017844-10A1
Application #
3151095
Study Section
Biopsychology Study Section (BPO)
Project Start
1978-07-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Stein, L J; Dorsa, D M; Baskin, D G et al. (1987) Reduced effect of experimental peripheral hyperinsulinemia to elevate cerebrospinal fluid insulin concentrations of obese Zucker rats. Endocrinology 121:1611-5
Corp, E S; Woods, S C; Porte Jr, D et al. (1986) Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci Lett 70:17-22
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Figlewicz, D P; Stein, L J; West, D et al. (1986) Intracisternal insulin alters sensitivity to CCK-induced meal suppression in baboons. Am J Physiol 250:R856-60

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