Hepatic Metabolic Changes in Response to Glucagon Infusion
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Hepatic lipid metabolism
研究概览
简要总结
The objective of the study is to investigate how exogenously administered glucagon affects hepatic lipid, glucose and protein metabolism as well as appetite, food intake and resting energy expenditure.
详细描述
Most research has focused on the role of the pancreatic hormone, insulin, and insulin signalling (or lack of) in the development of NAFLD. However, increasing evidence suggest that the other major gluco-regulatory pancreatic hormone glucagon is also implicated in lipid metabolism and recent human data from studies investigating the effect of glucagon receptor antagonism suggest that glucagon signalling may be essential for maintaining a fat-free liver. This, combined with observations of increased degree of hepatic steatosis in patients after total pancreatectomy, who are devoid of pancreatic glucagon and typically are lean and peripherally insulin sensitive, suggests that glucagon may play a hitherto unrecognised role in the pathophysiology of NAFLD.
The hypothesis of the study is that exogenously delivered glucagon will drive hepatic metabolism in a lipolytic direction and increase resting energy expenditure without affecting appetite and food intake.
The acute effects of exogeneous glucagon infusion on hepatic lipid metabolism will be evaluated in patients after total pancreatectomy (no endogenous pancreatic hormones), in patients with type 1 diabetes (no endogenous insulin production) and in healthy controls (preserved endogenous pancreatic hormones).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Pancreatectomised patients
- •Patients who have undergone total pancreatectomy
- •Caucasian between 30-80
- •Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
- •Informed consent
- •Patients with type 1 diabetes
- •Patients with C-peptide negative type 1 diabetes
- •Caucasian between 30-80
- •Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
- •Informed consent
- •Healthy controls
- •Normal fasting plasma glucose (< 7 mmol/l) and normal HbA1c (< 6.5 %) (30,31)
- •Normal blood haemoglobin (>8.3 mmol/l for males and >7.3 mmol/l for females)
- •Caucasian between 30-80
- •Informed consent
排除标准
- •All subjects
- •Inflammatory bowel disease
- •Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
- •Nephropathy (eGFR < 60 ml/min/1.73 m² and/or urine albumin > 20 mg/L)
- •Known liver disease (excluding non-alcoholic fatty liver disease)
- •Severe lung disease
- •Pregnancy and/or breastfeeding
- •Uncontrolled hypertension and/or significant cardiovascular disease
- •Treatment with drugs with potential steatogenic side-effects within three months prior to inclusion
- •Alcohol consumption above 21 units/week for men and 14 units/week for women
- •Any condition that the investigator feels would interfere with the safety of the trial participation or the safety of the subject.
研究组 & 干预措施
Glucagon
3 hours i.v. infusion of Glucagon (4 ng/kg/min).
干预措施: Glucagon (Drug)
Saline
3 hours i.v. infusion of saline
干预措施: Saline (Drug)
结局指标
主要结局
Hepatic lipid metabolism
时间窗: -120,-30,-15,0,30,60,90,120,135,150 minutes
evaluated using isotopic labelled tracer kinetics: lipolysis, ketogenesis, very low-density lipoprotein (VLDL) secretion and free fatty acid (FFA) re-esterification rate
次要结局
- Changes in resting energy expenditure and oxidation rate(0, 150 minutes)
- Food intake(30 minutes (150-180) minutes)
- Changes in appetite sensation(0,30,60,90,120,150 minutes)
- Changes in plasma concentration of amino acids(0, 60, 120, 150 minutes)
- Changes in plasma concentration of fibroblast growth factor 21 (FGF-21)(-120,0,150 minutes)
- Changes in plasma concentration of lipids(0, 60,150 minutes)
- Endogenous glucose production(-120,-30,-15,0,30,60,90,120,135,150 minutes)