The GLP-1-mediated Gut-kidney Axis
Conditions
Keywords
glucagon-like peptide-1, kidney, renal hemodynamics, renal blood flow
Brief summary
This study investigates the hypothesis, that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation.
Detailed description
Human studies have recently demonstrated a significant natriuretic effect of GLP-1 when the extracellular fluid volume (ECFV) is expanded by intravenous sodium-loading; in these studies, there was a suppression of ANG II with no change in net renal hemodynamics, pointing to a tubular mechanism for reduced NaCl reabsorption secondary to the ANG II suppression. In the current randomized and controlled study, investigators aim to test the hypothesis that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation. Thus, contributing to the renoprotective action of GLP-1. Under fixed sodium intake for 4 days before each study day, 10 healthy male participants will be investigated during a 1-hour infusion of GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Interleaved measurements of RAF, oxygenation (T2\*) and perfusion by arterial spin labeling in the renal cortex and medulla at fixed time points will be conducted, using Magnetic Resonance Imaging (MRI).
Interventions
Intravenous infusion (1.5 pmol/kg/min) for 60 min.
DRUGsaline 0.9%
Intravenous infusion for 60 min.
Sponsors
Department of Cardiovascular and Renal Research, University of Southern Denmark
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Normal health demonstrated by medical examination. * Normal values for fasting plasma glucose, total cholesterol, triglyceride, HDL, LDL, creatinine, AST, ALT and electrolyte concentrations.
Exclusion criteria
* Immunosuppressive treatment for the previous 12 months. * Alcohol abuse. * Medical treatment with oral glucocorticoids, dipeptidyl peptidase-4 (DPP-4) inhibitors, or GLP-1 receptor agonists that, in the opinion of the investigator, may interfere with glucose metabolism. * Use of lithium. * Medical treatment that affects insulin secretion or cardiovascular efficacy goals. * Liver disease (ALT\> 2 x normal value). * Renal impairment (creatinine\> 130 µM and / or albuminuria). * Severe claustrophobia. * MRI incompatible foreign bodies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| T2* signal | 1 hour | Changes in T2\* signal in renal cortex and medulla |
| Arterial Spin Labeled (ASL) | 1 hour | Changes in Arterial Spin Labeled (ASL) MRI Perfusion Imaging in renal cortex and medulla |
| Renal Artery Flow Phase (RAF) | 1 hour | Changes in Renal Artery Flow Phase (RAF)-Contrast Magnetic Resonance |
Countries
Denmark
Outcome results
None listed