CHOLECYSTIKININ SECRETION & ACTION IN PATIENT WITH INSULIN RESISTANCE

胆囊收缩素（CCK）是一种多肽激素， 在进食过程中，刺激胰腺外分泌 分泌、胆囊收缩和肠蠕动。 因为 在测量CCK血液水平的困难之前， 了解这种激素的生理和病理。 的 首席研究员最近开发了一种敏感的， 用于测量空腹和餐后的特异性生物测定 血浆CCK水平，并已证明，生理 CCK浓度通过以下方式直接调节β细胞功能 增强氨基酸诱导的胰岛素分泌。 而且他 非胰岛素依赖型糖尿病患者的初步研究 2型糖尿病（NIDDM）表现出CCK分泌异常， 喂养混合的流质食物。 这项拟议的研究将研究CCK在受损的 NIDDM胰岛素分泌研究 项目1中描述的患者及其家属群体。 CCK 分泌和作用将在以下对象中进行研究：（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）胰岛素抵抗者， 糖耐量异常者;（4）NIDDM患者。将 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 用CCK纠正。 最后， 确定是否存在CCK分泌的家族模式， 导致异常分泌的行为。

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.