The Underlying Mechanisms Regarding the Effect of Glucagon on the Kidneys Will be Investigated in Healthy Males.

Ali Asmar

Status

Enrolling

Conditions

Kidney Diseases

Treatments

Other: Placebo

Other: Glucagon and exendin 9-39

Other: Glucagon

Study type

Interventional

Funder types

Other

Identifiers

NCT06498063

NNF21OC0070308 (Other Grant/Funding Number)

20-1914 ( 21-1518;Other Grant/Funding Number)

H-22019483

Details and patient eligibility

About

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?

Full 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:

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.

Enrollment

10 estimated patients

Sex

Male

Ages

20 to 60 years old

Volunteers

Accepts Healthy Volunteers

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)

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Triple Blind

10 participants in 3 patient groups, including a placebo group

Glucagon

Experimental group

Description:

Glucagon infusion of 5 ng·kg-1·min-1 from 0-60 minutes and 10 ng·kg-1 ·min-1 from 60-120 minutes.

Treatment:

Other: Glucagon

Other: Glucagon and exendin 9-39

Other: Placebo

Glucagon+Exendin9-39

Experimental group

Description:

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).

Treatment:

Other: Glucagon

Other: Glucagon and exendin 9-39

Other: Placebo

Sodium chloride (Placebo comparator)

Placebo Comparator group

Description:

NaCl (0.9%)

Treatment:

Other: Glucagon

Other: Glucagon and exendin 9-39

Other: Placebo