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Impact of Ghrelin of Beta-cell Function and Insulin Sensitivity in Humans

生长素释放肽对人类 β 细胞功能和胰岛素敏感性的影响

基本信息

批准号：
7906865
负责人：
Jenny Tong
金额：
$ 17.7万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-25 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7906865
关键词：
Acute Adrenergic Agents Affect Agonist Alpha Cell Animals Arginine Beta Cell Body Weight Catecholamines Cell Line Cell physiology Cells Clinical Consensus Development Disease Dose Eating Enteral Epinephrine Gastrointestinal Motility Glucagon Glucose Goals Growth Hormone Receptor Hormones Human Hydrocortisone In Vitro Infusion procedures Injection of therapeutic agent Insulin Intravenous Islets of Langerhans Measures Pancreas Peptides Peripheral Physiological Plasma Rattus Regulation Relative (related person)Research Research Personnel Saline Sampling Secretory Cell Somatotropin Structure of beta Cell of islet Testing Time adrenergic blood glucose regulation clinically relevant design falls fasting plasma glucose ghrelin ghrelin receptor glucose metabolism human subject increased appetite insulin secretion insulin sensitivity intravenous glucose tolerance test islet motility disorder obesity treatment patient oriented research receptor wasting

项目摘要

DESCRIPTION (provided by applicant): This application is to provide protected time in order to perform patient oriented research with the goal of becoming an independent investigator studying the physiological and pharmacological functions of gut hormones and glucose metabolism. Ghrelin, a gut hormone, has been shown to inhibit pancreatic beta-cell insulin secretion and raise plasma glucose levels in humans, but it is unclear whether these are physiologic functions of ghrelin. Importantly, not much is known about the mechanism by which this occurs. The proposed research is designed to test the hypothesis that physiologic levels of ghrelin suppress insulin secretion and stimulate glucagon secretion in healthy human subjects and that this is an action of ghrelin on the islet, rather than one resulting indirectly from alterations in peripheral insulin sensitivity or from changes in counter-regulatory hormones (growth hormone [GH], catecholamines, and cortisol). Specific Aim 1: To determine the dose of ghrelin required to inhibit insulin secretion. Healthy human subjects will receive either ghrelin or saline infusion at three different doses. An intravenous glucose tolerance test will be used to assess insulin secretion. Specific Aim 2: To determine: a) whether ghrelin decreases insulin release by decreasing beta-cell sensitivity to glucose; b) whether ghrelin increases glucagon release by decreasing alpha-cell sensitivity to glucose. Detailed assessments of beta- and alpha-cell functions as well as peripheral insulin sensitivity will be performed using a frequently sampled intravenous glucose tolerance test and an arginine stimulation test in healthy subjects with normal fasting plasma glucose. Specific Aim 3: To measure the relative contribution of the counter-regulatory hormones to the effects of ghrelin on insulin secretion and insulin sensitivity by using either GH receptor blockade, combined beta- and alpha-adrenergic blockade, or infusion of cortisol in healthy subjects with normal fasting plasma glucose. The development of ghrelin agonists and ghrelin antagonists for treating body weight disorders makes understanding the mechanisms for their effects on glucose metabolism of clinical relevance.

描述（由申请人提供）：