Acute Effects of GLP-1 on Renal Hemodynamics

Acute Effects of GLP-1 on Renal Hemodynamics: Simultaneous Perfusion and Oxygenation Measurements in Cortex and Medulla Using Magnetic Resonance Imaging

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.

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).

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.