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| ID | Type | Description | Link |
|---|---|---|---|
| 20-1914; 21-1518 | Other Grant/Funding Number | Augustinus Fonden | |
| NNF21OC0070308 | Other Grant/Funding Number | Novo Nordisk Fonden |
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| Name | Class |
|---|---|
| University of Copenhagen | OTHER |
| The Augustinus Foundation, Denmark. | OTHER |
| The Novo Nordic Foundation | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glucagon | Experimental | Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes. |
|
| Glucagon+Exendin9-39 | Experimental | 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). |
|
| Sodium chloride (Placebo comparator) | Placebo Comparator | NaCl (0.9%) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glucagon | Other | Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Natriuresis | From urine samples, unit mmol/L | Analyzed from urine samples at -60, 0, 60 and 120 minutes |
| Glucagon extraction | From blood samples, unit pmol/L | Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Glomerular filtration rate | Unit mL/min | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ali Asmar, MD | Contact | 800-555-5555 | ali.asmar.02@regionh.dk | |
| Anna Billeschou Bomholt | Contact | 800-555-5555 | anna.billeschou@sund.ku.dk |
| Name | Affiliation | Role |
|---|---|---|
| Ali Asmar, MD | Bispebjerg Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Physiological laboratory, Bispebjerg Hospital, Research Unit, Clinical Physiology / Nuclear Medicine Department | Recruiting | Copenhagen | 2400 | Denmark |
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| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D005934 | Glucagon |
| C083773 | exendin (9-39) |
| ID | Term |
|---|---|
| D052336 | Proglucagon |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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| Placebo | Other | Placebo (0.9% NaCl). |
|
| Glucagon and exendin 9-39 | Other | 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). |
|
from urine samples, unit mL/min
| Analyzed from urine samples at -60, 0, 60 and 120 minutes |
| Renal Blood Flow | Unit mL/min | 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 | Analyzed from blood samples drawn at -30, 0, 20, 40, 60, 80, 100, 120, 140, 160 and 180 minutes |
| D052801 | Male Urogenital Diseases |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |