Glucagon, Ghrelin and Growth Hormone as Counterregulatory Hormones
试验速览
- 阶段
- 不适用
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Circulating acyl-ghrelin concentration after glucagon stimulation with and without beta-adrenergic blockade
研究概览
简要总结
Glucagon has been used for decades as a test of growth hormone (GH) reserve. The pathway by which GH is stimulated by glucagon is not established. Acyl ghrelin has been shown to increase GH levels and to be stimulated by an increase in adrenergic activity. The proposed study will test the concept that with the fall in blood glucose it is likely that there is a sympathetic discharge which contributes to the increase in acyl ghrelin and indirectly leads to the increase in GH and cortisol.
详细描述
Glucagon given to healthy adults in doses of 1-1.5 mg i.m. has been shown to result in a peak glucagon level in the circulation after 30 min, followed by an increase in glucose and insulin levels. The subsequent decline in glucose, insulin and glucagon was followed by an increase in cortisol and GH. Ghrelin is a 28 amino acid peptide which is released from the fundus of the stomach, within the oxyntic glands and the small intestine. It circulates in two major forms, acylated and des-acylated ghrelin. Acylated ghrelin has strong GH-releasing effects which are mediated via the G-protein coupled ghrelin receptor. The proposed study will test the concept that with the fall in blood glucose during a glucagon test it is likely that there is a sympathetic discharge which contributes to the increase in acyl ghrelin and indirectly leads to the increase in GH and cortisol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy normal men
- •Age 18-30 yrs
- •BMI 18-27 kg/m2
排除标准
- •Medication or previous surgery known to affect ghrelin secretion.
- •Medications known to have an impact on body weight (Seroquel, tricyclic antidepressants).
- •Medications known to have an impact on the beta adrenergic system.
- •Coronary artery disease, congestive heart failure, peripheral vascular disease, diabetes mellitus, significant hypertension (BP >180 systolic or >100 diastolic at rest); renal, hepatic, pulmonary disease; untreated hypothyroidism, untreated hyperthyroidism; history of seizure disorder; history of malignancy (other than some skin cancers), history of active chronic infections (e.g., HIV, tuberculosis).
- •Endocrine disorders, i.e., pheochromocytoma, adrenal insufficiency
- •Hematocrit < 41% men
- •History of daily tobacco use within past 3 months
- •Chronic alcohol abuse by history
- •Weight not stable (more than 10% weight change or more over past 6 months)
- •Strenuous exercise for average of more than 60 min/day
- •Investigational drug within past 6 weeks
- •Psychiatric history especially eating disorders
- •Transmeridian travel within 2 weeks prior to or during study
- •Known hypersensitivity to beta-blockers
- •Estimated Glomerular Filtration Rate below 60 mL/min/1.73m
- •Known cardiac dysrhythmia, especially first degree heart block. -
研究组 & 干预措施
Saline s.c. injection and placebo tablet
Saline s.c. injection and one placebo tablet (preceded by one placebo tablet per day at 0900h for two days before admission).
干预措施: Saline (Drug)
Saline s.c. injection and placebo tablet
Saline s.c. injection and one placebo tablet (preceded by one placebo tablet per day at 0900h for two days before admission).
干预措施: Placebo (Drug)
glucagon s.c. injection and placebo tablet
1 mg glucagon s.c. injection and one placebo tablet (preceded by one placebo tablet per day at 0900h for two days before admission).
干预措施: Glucagon (Drug)
glucagon s.c. injection and placebo tablet
1 mg glucagon s.c. injection and one placebo tablet (preceded by one placebo tablet per day at 0900h for two days before admission).
干预措施: Placebo (Drug)
Saline s.c. injection and atenolol tablet
Saline s.c. injection and 100 mg atenolol tablet
干预措施: Saline (Drug)
Saline s.c. injection and atenolol tablet
Saline s.c. injection and 100 mg atenolol tablet
干预措施: Atenolol (Drug)
glucagon s.c. injection and atenolol tablet
1 mg glucagon s.c. injection and 100 mg atenolol tablet
干预措施: Glucagon (Drug)
glucagon s.c. injection and atenolol tablet
1 mg glucagon s.c. injection and 100 mg atenolol tablet
干预措施: Atenolol (Drug)
结局指标
主要结局
Circulating acyl-ghrelin concentration after glucagon stimulation with and without beta-adrenergic blockade
时间窗: 18 months
次要结局
- Association between circulating acyl-ghrelin concentration and GH and cortisol after glucagon administration with and without beta-adrenergic blockade(18 months)
研究者
Michael Thorner, MD
MD
University of Virginia