Regulation of Food Intake and Body Weight by Amylin

胰淀素对食物摄入量和体重的调节

• 批准号: 6786589
• 负责人: ROGER REIDELBERGER
• 金额: $ 17.91万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786589
• 关键词: amylin; anorexia; bioenergetics; biological signal transduction; body weight; cachexia; cholecystokinin; hormone receptor; hormone regulation /control mechanism; hypothalamus; insulin; laboratory mouse; laboratory rat; leptin; malnutrition; neurons; neuroregulation; nutrient intake activity; nutrition related tag; obesity; pancreas neoplasms; pathologic process; peptide hormone biosynthesis; satiations

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.

胰淀素（也称为胰岛淀粉样多肽或IAPP）是一种37个氨基酸的肽，其与胰岛素共同产生并从胰腺分泌，以响应膳食。 胰淀素也存在于肠内分泌细胞、内脏感觉神经元和下丘脑中。 当全身给药或给药到大鼠脑中时，胰淀素有效地减少食物摄入、体重和/或肥胖。 相比之下，已报道使用AC 187的胰淀素受体阻断剂增加食物摄入和肥胖。 有针对性地破坏胰淀素基因的小鼠在4个月大时体重增加了29%。 总之，这些结果表明，胰淀素在控制食物摄入和长期调节能量储备方面起着至关重要的作用。 因此，推测胰淀素产生不足或胰淀素不敏感性可能导致肥胖的发展是合理的。 胰淀素还可能在与胰腺癌相关的营养不良中发挥病理生理作用，因为血浆胰淀素的显著升高与胰腺癌患者的早期严重恶病质相关。研究旨在验证胰腺胰淀素作为大脑激素信号以减少食物摄入和调节脂肪能量储备的假设。 将使用大鼠和胰淀素无效突变小鼠模型来检验该假设。具体目标是：1。确定胰淀素是否作为一种基本的激素信号（通过血液），以减少食物摄入量，体重和肥胖。2.确定血浆胰淀素对摄入（或胃内输注）不同营养素的反应是否足以减少食物摄入和体重。3.确定胰淀素是否通过与CCK和瘦素的协同作用减少食物摄入量、体重和肥胖，已知这些肽有助于产生饱腹感和长期调节能量储备。4.确定内源性胰淀素作用的来源和部位是否在外周和/或大脑中，以减少食物摄入、体重和肥胖。这些研究将促进我们对胰淀素在控制食物摄入和长期调节能量储备方面的生理作用的理解。 它们也可能为寻找饮食和代谢紊乱的致病机制及其治疗策略提供方向。