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| Name | Class |
|---|---|
| University of Southern Denmark | OTHER |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| human glucagon-like peptide-1 | Active Comparator | Intervention: Drug: human glucagon-like peptide-1 Other names: GLP-1 |
|
| Placebo | Placebo Comparator | Intervention: Drug: Placebo (saline) Other names: Placebo for human glucagon-like peptide-1 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glucagon-Like Peptide 1 | Drug | Intravenous infusion (1.5 pmol/kg/min) for 60 min. |
|
| Measure | Description | Time Frame |
|---|---|---|
| T2* signal | Changes in T2* signal in renal cortex and medulla | 1 hour |
| Arterial Spin Labeled (ASL) | Changes in Arterial Spin Labeled (ASL) MRI Perfusion Imaging in renal cortex and medulla | 1 hour |
| Renal Artery Flow Phase (RAF) | Changes in Renal Artery Flow Phase (RAF)-Contrast Magnetic Resonance | 1 hour |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ali Asmar, MD, PhD | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet - Glostrup | Glostrup Municipality | Copenhagen | 2600 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17928588 | Background | Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. doi: 10.1152/physrev.00034.2006. | |
| 17475961 | Background | Korner M, Stockli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007 May;48(5):736-43. doi: 10.2967/jnumed.106.038679. |
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| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
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| saline 0.9% | Drug | Intravenous infusion for 60 min. |
|
|
| 24467746 | Background | Pyke C, Heller RS, Kirk RK, Orskov C, Reedtz-Runge S, Kaastrup P, Hvelplund A, Bardram L, Calatayud D, Knudsen LB. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014 Apr;155(4):1280-90. doi: 10.1210/en.2013-1934. Epub 2014 Jan 27. |
| 25670826 | Background | Asmar A, Simonsen L, Asmar M, Madsbad S, Holst JJ, Frandsen E, Moro C, Jonassen T, Bulow J. Renal extraction and acute effects of glucagon-like peptide-1 on central and renal hemodynamics in healthy men. Am J Physiol Endocrinol Metab. 2015 Apr 15;308(8):E641-9. doi: 10.1152/ajpendo.00429.2014. Epub 2015 Feb 10. |
| 26956188 | Background | Asmar A, Simonsen L, Asmar M, Madsbad S, Holst JJ, Frandsen E, Moro C, Sorensen CM, Jonassen T, Bulow J. Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy. Am J Physiol Endocrinol Metab. 2016 May 1;310(9):E744-53. doi: 10.1152/ajpendo.00518.2015. Epub 2016 Mar 8. |
| 28174344 | Background | Asmar A, Asmar M, Simonsen L, Madsbad S, Holst JJ, Hartmann B, Sorensen CM, Bulow J. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men. Physiol Rep. 2017 Feb;5(3):e13073. doi: 10.14814/phy2.13073. |
| 23463656 | Background | Skov J, Dejgaard A, Frokiaer J, Holst JJ, Jonassen T, Rittig S, Christiansen JS. Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men. J Clin Endocrinol Metab. 2013 Apr;98(4):E664-71. doi: 10.1210/jc.2012-3855. Epub 2013 Mar 5. |
| 30835273 | Background | Asmar A, Cramon PK, Simonsen L, Asmar M, Sorensen CM, Madsbad S, Moro C, Hartmann B, Jensen BL, Holst JJ, Bulow J. Extracellular Fluid Volume Expansion Uncovers a Natriuretic Action of GLP-1: A Functional GLP-1-Renal Axis in Man. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519. doi: 10.1210/jc.2019-00004. |
| 36734354 | Derived | Haddock B, Kristensen KB, Tayyab M, Larsson HBW, Lindberg U, Vestergaard M, Francis S, Jensen BL, Andersen UB, Asmar A. GLP-1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading. J Am Heart Assoc. 2023 Feb 7;12(3):e027712. doi: 10.1161/JAHA.122.027712. Epub 2023 Feb 3. |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |