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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
10
Selective antagonist of the GIPR, GIP(3-30)NH2
Selective antagonist of the GLP-2R, GLP-2(3-33)
Saline
Rigshospitalet
Copenhagen, Denmark
Redistribution of splanchnic blood flow (functional MRI)
Flow in mesenteric superior artery
Time frame: 90 minutes
GIP levels
Blood sample (pmol/L)
Time frame: 90 minutes
GLP-2 levels
Blood sample (pmol/L)
Time frame: 90 minutes
GIP(3-30)NH2 levels
Blood sample (nmol/L)
Time frame: 90 minutes
GLP-2(1-33) levels
Blood sample (nmol/L)
Time frame: 90 minutes
CTX (bone resorption marker)
Blood sample
Time frame: 90 minutes
P1NP (bone formation marker)
Blood sample
Time frame: 90 minutes
Glucose
Blood sample (mmol/L)
Time frame: 90 minutes
C-peptide
Blood sample (pmol/L)
Time frame: 90 minutes
Insulin
Blood sample (pmol/L)
Time frame: 90 minutes
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Glucagon
Blood sample (pmol/L)
Time frame: 90 minutes
Heart rate
Beats/minute
Time frame: 90 minutes
Flow in coeliac trunk
Functional MRI estimated blood flow
Time frame: 90 minutes
Flow in hepatic artery
Functional MRI estimated blood flow
Time frame: 90 minutes
Flow in portal vein
Functional MRI estimated blood flow
Time frame: 90 minutes
Liver oxygen content
Functional MRI estimated oxygenation
Time frame: 90 minutes