Behavioral and neural measures of oral carbohydrate and sweetener reward signals

口服碳水化合物和甜味剂奖励信号的行为和神经测量

• 批准号: 10532978
• 负责人: Paul A. S Breslin
• 金额: $ 23.29万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10532978
• 关键词: American; Area; Behavioral; Blood Glucose; Brain; Brush Border; Calories; Carbohydrates; Cells; Consumption; Data; Detection; Diabetes Mellitus; Disaccharidases; Disaccharides; Energy Intake; Enhancers; Enzyme Inhibitor Drugs; Enzymes; Fructose; Glucokinase; Glucose; Glucose Transporter; Glycosides; Human; Ingestion; Insulin; Intake; Islet Cell; Mammals; Measures; Membrane; Metabolic; Metabolic Control; Metabolic Pathway; Metabolic syndrome; Metabolism; Monosaccharides; Motivation; Mus; OGTT; Obesity; Oral; Oral cavity; Organ; Pancreas; Pathway interactions; Pattern; Perception; Pharmacology; Plasma; Play; Potassium Channel; Psychophysics; Rattus; Research; Rewards; Rodent; Role; Running; Signal Pathway; Signal Transduction; Stimulus; Sucrose; Sweetening Agents; Taste Buds; Taste Perception; Testing; Therapeutic; Visceral; brain reward regions; conditioned place preference; glucose tolerance; improved; inhibitor; insulin secretion; interest; motivated behavior; neurophysiology; preference; prevent; relating to nervous system; response; sugar; sweet taste perception; taste stimuli

Abstract The metabolic signaling pathway in T1r3+ mouse taste cells are similar to that found in pancreatic beta islet cells that sense calories from glucose. This signaling pathway is comprised of glucose transporters (GLUTs & SGLTs), glucokinase, and the ATP-gated potassium channel (KATP). Human taste cells have a similar pathway. The oral disaccharidase enzymes, first found in the brush border of the gut, that sever glycosidic bonds are expressed orally in rodents; but, beyond our unpublished preliminary data, this has not been shown in humans. We hypothesize that oral disaccharidases are necessary to free glucose and other monosaccharides to activate the metabolic signaling pathway. We also hypothesize that these enzymes in humans enable the metabolic responses of taste cells to contribute to transduction and perception of disaccharide taste. We propose that this results in stronger preferences for disaccharides over non-caloric sweeteners. We hypothesize further that the release of glucose from disaccharide cleaving, its transport into taste cells, and its metabolism to generate ATP leads to taste signaling. This signal may also contribute to anticipatory metabolic responses in humans during carbohydrate tolerance tests. In Aim 1 we will determine whether oral metabolic signaling contributes to disaccharide perception, metabolic tolerance, liking and preference in humans. In Aim 2 we will determine whether oral metabolic signals influence licking and motivated behaviors in rats and where in the brain these signals are registered. If sugar reward signaling can be manipulated by modulating oral disaccharidase activity, then there should be therapeutic utility to developing a strategy to maximize reward while reducing sugar intake. Improving our understanding of the role oral glucose metabolic signaling plays in human taste should help prevent and reduce obesity, diabetes, and metabolic syndrome that afflict approximately one-third of all Americans.

摘要 T1 r3+小鼠味觉细胞中的代谢信号通路与胰岛β细胞中发现的代谢信号通路相似 能够感知葡萄糖中的卡路里该信号通路由葡萄糖转运蛋白（GLUT和SGLT）组成， 葡萄糖激酶和ATP门控钾通道（KATP）。人类的味觉细胞也有类似的途径。口腔 首先在肠道刷状缘发现的切断糖苷键的二磷酸脱氢酶表达， 口服啮齿动物;但是，除了我们未发表的初步数据，这还没有在人类中显示。我们 假设口服二硫代磷酸酶是释放葡萄糖和其他单糖以激活 代谢信号通路我们还假设，人体内的这些酶使代谢 味觉细胞的反应有助于二糖味觉的转导和感知。我们建议， 导致对二糖的偏好超过无热量甜味剂。我们进一步假设， 从二糖裂解中释放葡萄糖，将其转运到味觉细胞中，并代谢产生ATP 导致味觉信号。该信号也可能有助于人类在治疗期间的预期代谢反应 碳水化合物耐量试验在目标1中，我们将确定口服代谢信号是否有助于 二糖感知、代谢耐受性、喜好和偏好。在目标2中，我们将确定 口腔代谢信号是否会影响大鼠的舔和动机行为，以及这些信号在大脑中的位置。 信号被记录。如果糖奖赏信号可以通过调节口服二氢腺苷酸酶活性来操纵， 那么，在减少糖摄入的同时，开发一种最大化奖励的策略应该是有治疗效用的。 提高我们对口服葡萄糖代谢信号在人类味觉中所起作用的理解应该有助于 预防和减少肥胖、糖尿病和代谢综合征，这些疾病困扰着大约三分之一的人口， 美国人