Renal Extraction of Glucagon and Renal Effects of Glucagon
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Glucagon extraction
Study Overview
Brief Summary
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?
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- 20 Years to 60 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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
Exclusion Criteria
- •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)
Outcomes
Primary Outcomes
Glucagon extraction
Time Frame: 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
Time Frame: Analyzed from urine samples at -60, 0, 60 and 120 minutes
From urine samples, unit mmol/L
Secondary Outcomes
- 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)
Investigators
Ali Asmar
Chief Physician, Associate Professor, PhD, MD
Bispebjerg Hospital