Healthy
Conditions
Brief summary
The objective of the study is to delineate the glucagonotropic signal exerted by selected amino acids in human subjects as well as the metabolic clearance rate of these amino acids after intravenous infusion
Detailed description
After being informed about the study and the potential risks, each participant giving written informed consent will participate in six experimental days. The glucagonotropic effect and metabolic clearance of selected amino acids and saline (placebo), respectively, will be evaluated in 12 healthy individuals. After screening, each participant will undergo 6 double-blinded experimental days performed in randomized order. The experimental days will each last 75 minutes. The amino acids selected for the experiment are glutamine, arginine, alanine, leucine and proline.
Interventions
OTHERAmino acid bolus infusion
Equimolar bolus infusions of amino acids or saline (placebo)
Sponsors
The Novo Nordisk Foundation Center for Basic Metabolic Research
University Hospital, Gentofte, Copenhagen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
randomized, double-blinded, single-arm study. Participants act as their own controls.
Eligibility
Sex/Gender
MALE
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* normal fasting plasma glucose and glycated hemoglobin (HbA1c) \< 42 mmol/mol * body mass index (BMI) between 18.5 and 25 kg/m2 * Hemoglobin \> 8.3 mmol/L * Age between 20 and 65 years * oral and written informed consent
Exclusion criteria
* Diabetes * first-degree relatives with diabetes * fasting plasma triglycerides indicating dyslipidemia (\> 2 mmol/L) * nephropathy (eGFR \< 60 ml/min) and/or microalbuminuria (albumine/creatinine ratio \> 30 microgram/mg) * liver disease and/or ALT and/or AST levels \> 2 x upper normal reference limits. * signs of liver fibrosis and/or steatosis evaluated by transient elastography (CAP \> 238 dB/min) and/or kPa \> 6.0) and/or FIB-4 index \> 1.45 * regular use of prescription medication * use of dietary protein supplementation * any condition the investigator feels would interfere with trial completion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| bsAUC30 | bsAUC is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min and 30 min | Baseline subtracted area under the curve for glucagon concentration during the first 30 minutes of the experiment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC30 | AUC30 is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min and 30 min | total area under the curve for glucagon concentration during the first 30 minutes of the experiment |
| AUC60 | AUC60 is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min, 30 min and 60 min | total area under the curve for glucagon concentration the first 60 minutes of the experiment |
| bsAUC60 | bsAUC60 is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min, 30 min and 60 min | Baseline subtracted area under the curve for glucagon concentration during the first 60 minutes of the experiment |
| peak glucagon concentration | measured between time 0 min and time 60 min | the highest concentration of glucagon after infusion of amino acids/placebo |
Other
| Measure | Time frame | Description |
|---|---|---|
| Metabolic clearance of amino acids | Time 0 min to time 60 min | The metabolic clearance of each infused amino acid calculated from amino acid concentrations |
| GIP | Time -15 min to time 60 min | plasma concentration of glucose-dependent insulinotropic polypeptide (GIP) during the experiment |
| Insulin | Time -15 min to time 60 min | plasma concentration of insulin during the experiment |
| C-peptide | Time -15 min to time 60 min | plasma concentration of C-peptide during the experiment |
| Total and individual amino acids | Time -15 min to time 60 min | plasma concentration of total and individual amino acids during the experiment |
| GLP-1 | Time -15 min to time 60 min | plasma concentration of glucagon-like peptide 1 (GLP-1) during the experiment |
Countries
Denmark
Outcome results
None listed