CHOLECYSTIKININ SECRETION & ACTION IN PATIENT WITH INSULIN RESISTANCE

胆囊收缩素分泌

• 批准号: 3897564
• 负责人: ROGER A LIDDLE
• 金额: --
• 依托单位: MOUNT ZION HOSPITAL AND MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3897564
• 关键词: aminoacid; bioassay; cholecystokinin; diet; gallbladder; glucose tolerance test; hormone receptor; hormone regulation /control mechanism; human population genetics; human subject; hyperglycemia; insulin; insulin sensitivity /resistance; intravenous administration; laboratory rat; muscle contraction; noninsulin dependent diabetes mellitus; nutrition related tag; pancreatic islet function; pancreatic islets; plasma; radioimmunoassay; secretion; stomach emptying

Cholecystokinin (CCK), a polypeptide hormone that is released from the intestine during feeding, stimulates pancreatic exocrine secretion, gallbladder contraction, and bowel motility. Because of prior difficulties in measuring blood levels of CCK, little is known about the physiology and pathology of the hormone. The principal investigator has recently developed a sensitive and specific bioassay for measuring both fasting and postprandial plasma levels of CCK and has demonstrated that physiological concentrations of CCK directly regulate beta cell function by potentiating amino acid-induced insulin secretion. Moreover, his preliminary studies in patients with non-insulin dependent diabetes mellitus (NIDDM) demonstrate abnormal CCK secretion in response to feeding a mixed liquid meal. The proposed research will examine the role of CCK in the impaired insulin secretion of NIDDM by investigating four well characterized groups of patients and their families described in Project 1. CCK secretion and action will be studied in: (1) non-diabetic subjects with relative insulin sensitivity, (2) non-diabetic subjects with relative insulin resistance, (3) those with insulin resistance and abnormal glucose tolerance, and (4) those with NIDDM. It will be determined whether there is an abnormality in either CCK secretion, or beta cell resistance to the actions of CCK in patients with impaired insulin secretion and whether such a defect can be corrected by the administration of CCK. Finally, it will be determined whether there are familial patterns of CCK secretion or action that contribute to abnormal secretion.

胆囊收缩素 (CCK) 是一种多肽激素，由 进食时肠道，刺激胰腺外分泌 分泌、胆囊收缩和肠蠕动。 因为 以前测量 CCK 血液水平的困难很少 了解激素的生理学和病理学。 这 首席研究员最近开发了一种敏感且 用于测量空腹和餐后的特定生物测定 CCK 的血浆水平，并已证明生理学 CCK 浓度直接调节 β 细胞功能 增强氨基酸诱导的胰岛素分泌。 而且，他的 非胰岛素依赖型糖尿病患者的初步研究 mellitus (NIDDM) 表现出异常的 CCK 分泌响应 喂养混合流质餐。 拟议的研究将探讨 CCK 在受损患者中的作用 通过研究四个明确表征的 NIDDM 的胰岛素分泌 项目 1. CCK 中描述的患者群体及其家属 将在以下对象中研究分泌和作用：(1)非糖尿病受试者 具有相对胰岛素敏感性，（2）非糖尿病受试者 相对胰岛素抵抗，（3）有胰岛素抵抗的人以及 糖耐量异常；(4) NIDDM 患者。这将是 确定CCK分泌是否存在异常， 或 β 细胞对 CCK 作用的抵抗 胰岛素分泌受损以及这种缺陷是否可以修复 通过 CCK 管理进行纠正。 最后，将会是 确定 CCK 分泌是否存在家族模式或 导致异常分泌的作用。