Blood Flow
Conditions
Keywords
Gut hormones, GIP, GLP-2, Physiology
Brief summary
This project will describe the mechanisms of action and the relative contributions of GIP and GLP-2 to changes in gastrointestinal blood flow induced by oral glucose, exogenous GIP and GLP-2 infusions, and endogenous GIP and GLP-2 with the use of two novel receptor antagonists GIP(3-30)NH2 and GLP-2(3-33) in healthy individuals.
Detailed description
Each participant will attend eight independent randomised experimental days in the MRI-scanner with intravenous infusion (hormone/placebo), subcutaneous injection (hormon/placebo) and oral ingestion (glucose/water). On experimental day A-C, an intravenous infusion of saline, GIP(3-30)NH2, or GLP-2(3-33), respectively, starts at time point -20 minutes. On experimental day D-F, the same infusions are combined with an oral glucose tolerance test (75 gram of glucose dissolved in 250 ml water ingested orally) at time point 0 minutes. On experimental days G-H, a subcutaneous injection of either GIP or GLP-2 at time point 0 minutes is performed (positive control) during saline infusion and oral water ingestion. MRI measurements are repeatedly performed and blood samples are drawn to be analysed for endocrine responses from the intestines, pancreas, and bones.
Interventions
Selective antagonist of the GIPR, GIP(3-30)NH2
Selective antagonist of the GLP-2R, GLP-2(3-33)
Saline
Sponsors
Study design
Intervention model description
Single blind, placebo controlled, randomized, crossover study
Eligibility
Inclusion criteria
* No first degree relatives with diabetes * BMI 20-27 kg/m2
Exclusion criteria
* Not MRI-compatible implants * Claustrophobia * Diabetes * Abnormal kidney or liver function * Anemia * Planned weight loss or change in diet * Hypertension * Other conditions that could be expected to affect the primary or secondary outcomes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Redistribution of splanchnic blood flow (functional MRI) | 90 minutes | Flow in mesenteric superior artery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GLP-2 levels | 90 minutes | Blood sample (pmol/L) |
| GIP(3-30)NH2 levels | 90 minutes | Blood sample (nmol/L) |
| GLP-2(1-33) levels | 90 minutes | Blood sample (nmol/L) |
| CTX (bone resorption marker) | 90 minutes | Blood sample |
| P1NP (bone formation marker) | 90 minutes | Blood sample |
| Glucose | 90 minutes | Blood sample (mmol/L) |
| C-peptide | 90 minutes | Blood sample (pmol/L) |
| GIP levels | 90 minutes | Blood sample (pmol/L) |
| Glucagon | 90 minutes | Blood sample (pmol/L) |
| Heart rate | 90 minutes | Beats/minute |
| Flow in coeliac trunk | 90 minutes | Functional MRI estimated blood flow |
| Flow in hepatic artery | 90 minutes | Functional MRI estimated blood flow |
| Flow in portal vein | 90 minutes | Functional MRI estimated blood flow |
| Liver oxygen content | 90 minutes | Functional MRI estimated oxygenation |
| Insulin | 90 minutes | Blood sample (pmol/L) |
Countries
Denmark