Amylin (also called Islet Amyloid Polypeptide or IAPP) is a 37 amino acid peptide that is co-produced and secreted with insulin from the pancreas in response to a meal. Amylin is also found in gut endocrine cells, visceral sensory neurons, and hypothalamus. When administered systemically or into the brain of rats amylin potently reduces food intake, body weight and/or adiposity. In contrast, amylin receptor blockade using AC187 has been reported to increase food intake and adiposity. Mice with targeted destruction of the amylin gene develop a 29 percent larger body weight at 4 months of age. Together, these results suggest that amylin plays an essential role in control of food intake and long-term regulation of energy reserves. Thus, it is reasonable to speculate that insufficient amylin production or amylin-insensitivity may contribute to the development of obesity. Amylin may also play a pathophysiological role in the malnutrition associated with pancreatic cancer, because marked elevation of plasma amylin occurs in association with the early, severe cachexia in pancreatic cancer patients. Studies are designed to test the hypothesis that pancreatic amylin acts as a hormonal signal to the brain to reduce food intake and to regulate adipose energy reserves. Rat and amylin- null mutant mouse models will be used to test this hypothesis.
Specific aims are to: 1. Determine whether amylin acts as an essential hormonal signal (via the bloodstream) to decrease food intake, body weight, and adiposity. 2. Determine whether plasma amylin responses to ingestion (or intragastric infusion) of different nutrients are sufficient to decrease food intake and body weight. 3. Determine whether amylin reduces food intake, body weight, and adiposity through a synergistic interaction with CCK and leptin, peptides known to contribute to the production of satiety and the long-term regulation of energy reserves. 4. Determine whether the source and site of endogenous amylin action to reduce food intake, body weight, and adiposity is in the periphery and/or brain. These studies should advance our understanding of the physiological role of amylin in control of food intake and the long-term regulation of energy reserves. They may also provide direction in the search for pathogenic mechanisms of eating and metabolic disorders and strategies for their treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK055830-02S1
Application #
6796116
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Yanovski, Susan Z
Project Start
2001-09-15
Project End
2006-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$21,518
Indirect Cost
Name
Creighton University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
053309332
City
Omaha
State
NE
Country
United States
Zip Code
68178
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Olsson, Madelene; Herrington, Margery K; Reidelberger, Roger D et al. (2007) Comparison of the effects of chronic central administration and chronic peripheral administration of islet amyloid polypeptide on food intake and meal pattern in the rat. Peptides 28:1416-23
Chelikani, Prasanth K; Haver, Alvin C; Reidelberger, Roger D (2007) Effects of intermittent intraperitoneal infusion of salmon calcitonin on food intake and adiposity in obese rats. Am J Physiol Regul Integr Comp Physiol 293:R1798-808
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Chelikani, Prasanth K; Haver, Alvin C; Reidelberger, Roger D (2006) Dose-dependent effects of peptide YY(3-36) on conditioned taste aversion in rats. Peptides 27:3193-201
Chelikani, Prasanth K; Haver, Alvin C; Reidelberger, Roger D (2005) Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 288:R1695-706
Chelikani, Prasanth K; Haver, Alvin C; Reidelberger, Roger D (2005) Intravenous infusion of peptide YY(3-36) potently inhibits food intake in rats. Endocrinology 146:879-88

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