The Role of GIP and GLP-2 in Postprandial Splanchnic Blood Flow Distribution and Metabolism

Not Applicable

Completed

Interventions: Other: GLP-2R antagonist / study tool
Other: GIPR antagonist / study tool
Other: Placebo

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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
GLA-WAT	Placebo	GLP-2R antagonist infusion, saline injection, water ingestion
SAL-GLP-2	Placebo	Saline infusion, GLP-2 injection, water ingestion
GIA-WAT	Placebo	GIPR antagonist infusion, saline injection, water ingestion
GLA-WAT	GLP-2R antagonist / study tool	GLP-2R antagonist infusion, saline injection, water ingestion
GLA-GLU	GLP-2R antagonist / study tool	GLP-2R antagonist infusion, saline injection, glucose ingestion
SAL-GIP	Placebo	Saline infusion, GIP injection, water ingestion
GIA-WAT	GIPR antagonist / study tool	GIPR antagonist infusion, saline injection, water ingestion
SAL-WAT	Placebo	Saline infusion, saline injection, water ingestion
SAL-GLU	Placebo	Saline infusion, saline injection, glucose ingestion
GIA-GLU	GIPR antagonist / study tool	GIPR antagonist infusion, saline injection, glucose ingestion

Primary Outcome Measures

Name	Time	Method
Redistribution of splanchnic blood flow (functional MRI)	90 minutes	Flow in mesenteric superior artery

Secondary Outcome Measures

Name	Time	Method
Glucagon	90 minutes	Blood sample (pmol/L)
Flow in coeliac trunk	90 minutes	Functional MRI estimated blood flow
CTX (bone resorption marker)	90 minutes	Blood sample
Heart rate	90 minutes	Beats/minute
Flow in hepatic artery	90 minutes	Functional MRI estimated blood flow
GLP-2 levels	90 minutes	Blood sample (pmol/L)
GLP-2(1-33) levels	90 minutes	Blood sample (nmol/L)
C-peptide	90 minutes	Blood sample (pmol/L)
Insulin	90 minutes	Blood sample (pmol/L)
GIP(3-30)NH2 levels	90 minutes	Blood sample (nmol/L)
Liver oxygen content	90 minutes	Functional MRI estimated oxygenation
Glucose	90 minutes	Blood sample (mmol/L)
GIP levels	90 minutes	Blood sample (pmol/L)
P1NP (bone formation marker)	90 minutes	Blood sample
Flow in portal vein	90 minutes	Functional MRI estimated blood flow