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?
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
10
Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.
Placebo (0.9% NaCl).
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).
Physiological laboratory, Bispebjerg Hospital, Research Unit, Clinical Physiology / Nuclear Medicine Department
Copenhagen, Denmark
RECRUITINGNatriuresis
From urine samples, unit mmol/L
Time frame: Analyzed from urine samples at -60, 0, 60 and 120 minutes
Glucagon extraction
From blood samples, unit pmol/L
Time frame: Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes
Glomerular filtration rate
Unit mL/min
Time frame: 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
from urine samples, unit mL/min
Time frame: Analyzed from urine samples at -60, 0, 60 and 120 minutes
Renal Blood Flow
Unit mL/min
Time frame: 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
Unit mg/dL
Time frame: Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes
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