Renal Extraction of Glucagon and Renal Effects of Glucagon
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Glucagon extraction
研究概览
简要总结
The goal of this crossover study is to investigate to what extend glucagon affects the kidneys. The main questions it aims to answer are:
Does glucagon regulate kidney function through extraction in the kidney in addition to glomerular filtration? Does glucagon regulate kidney function by increasing renal plasma flow and glomerular filtration rate? Does glucagon regulate kidney function by increasing renal salt excretion?
详细描述
In patients with type 2 diabetes mellitus, plasma concentrations of glucagon are inappropriately high (hyperglucagonemia). Hyperglucagonemia has been speculated to contribute to the pathophysiology of diabetic kidney disease. Previously, glucagon has been assumed to cause glomerular hyperfiltration associated with urinary excretion of small proteins, a characteristic of early type 2 diabetic kidney injury. Further, glucagon has been shown to acutely increase urinary excretion of urea, sodium, and potassium, and patients with end-stage renal disease have elevated plasma levels of glucagon.
The purpose of this study is to clarify the underlying mechanisms behind the physiological effects of glucagon on kidney function and the kidney's ability to clear glucagon from the blood in healthy males. Specifically, the investigators aim to answer the following questions:
Does glucagon regulate kidney function through extraction in the kidney in addition to glomerular filtration? Does glucagon regulate kidney function by increasing renal plasma flow and glomerular filtration rate? Does glucagon regulate kidney function by increasing renal salt excretion?
The renal extraction of glucagon and the renal effects of glucagon will be investigated during a constant glucagon infusion in 10 healthy men aged 20-60 years. The study will be placebo-controlled. Each subject will participate in three independent and randomized trial days with a washout period of at least four weeks.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age: 20-60 years
- •Normal health ascertained through questioning and medical examination
- •Normal values for blood concentrations of fasting plasma glucose, fasting plasma total cholesterol, fasting triglycerides, HDL, LDL, creatinine, liver function, and electrolytes
- •Informed consent
排除标准
- •Immunosuppressive treatment in the preceding 12 months
- •Alcohol abuse
- •Medical treatment with oral glucocorticoids, dipeptidyl peptidase-4 (DPP-4) inhibitors, or GLP-1 receptor agonists, which, in the opinion of the investigator, may interfere with glucose metabolism
- •Use of lithium
- •Medical treatment that affects insulin secretion or cardiovascular performance measures
- •Liver disease (ALT > 2x normal value)
- •Renal impairment (se-creatinine > 130 μM and/or albuminuria)
研究组 & 干预措施
Glucagon
Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.
干预措施: Glucagon (Other)
Glucagon
Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.
干预措施: Placebo (Other)
Glucagon
Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.
干预措施: Glucagon and exendin 9-39 (Other)
Glucagon+Exendin9-39
Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).
干预措施: Placebo (Other)
Glucagon+Exendin9-39
Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).
干预措施: Glucagon and exendin 9-39 (Other)
Sodium chloride (Placebo comparator)
NaCl (0.9%)
干预措施: Placebo (Other)
Sodium chloride (Placebo comparator)
NaCl (0.9%)
干预措施: Glucagon and exendin 9-39 (Other)
Sodium chloride (Placebo comparator)
NaCl (0.9%)
干预措施: Glucagon (Other)
Glucagon+Exendin9-39
Glucagon (infusion of 5 ng·kg-1·min-1 from 0-60 minutes) and glucagon (infusion of 10 ng·kg-1 ·min-1 from 60-120 minutes) + a GLP-1R antagonist, exendin 9-39 (900 pmol·kg-1·min-1 from -30-120 minutes).
干预措施: Glucagon (Other)
结局指标
主要结局
Glucagon extraction
时间窗: Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes
From blood samples, unit pmol/L
Natriuresis
时间窗: Analyzed from urine samples at -60, 0, 60 and 120 minutes
From urine samples, unit mmol/L
次要结局
- Glomerular filtration rate(Measured via Fick's principle during steady state using [99mTc]Tc-DTPA (diethylene-triamine-pentaacetate) as a tracer given as a constant infusion from -210 to 180 min.)
- Diuresis(Analyzed from urine samples at -60, 0, 60 and 120 minutes)
- Renal Blood Flow(Measured via Fick's principle during steady state using [99mTc]Tc-DTPA (diethylene-triamine-pentaacetate) as a tracer given as a constant infusion from -210 to 180 min.)
- Urea(Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes)
研究者
Ali Asmar
Chief Physician, Associate Professor, PhD, MD
Bispebjerg Hospital