Intact Vagal Innervation for and Glucagon-like Peptide-1 (GLP-1) Effects

Study Overview
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Brief Summary
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The aim of this study is to investigate the role of transmission via the vagal nerve for the effect of glucose and Glucagon-like peptide-1 (GLP-1) in respect to insulin secretion. The hypothesis is that a great deal of the effects of GLP-1 is mediated via the nervous system and for this reason the investigators will research individuals with and without intact nervous supply.

Detailed Description
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GLP-1 is a potent enterogastron and incretin hormone. It is rapidly inactivated by dipeptidyl peptidase IV so only 10-15% enters the systemic circulation. This has led to the hypothesis that GLP-1 interact locally with afferent sensory nerve fibers. We investigated the role of intact vagal innervations on the effect of glucose and GLP-1 on the insulin secretion

Official Title
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The Significances of Intact Vagal Innervation for the Glucose and GLP1 Induced Insulin Secretion

Conditions
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Vagotomy, Truncal

Intervention / Treatment
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* Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor
* Other: oral glucose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: normal fasting plasma glucose normal hemoglobin informed consent Exclusion Criteria: type 1 diabetes mellitus or type 2 diabetes mellitus body mass index > 30 inflammatory bowel disease intestinal surgery serum creatinine > 250 µM and/or albuminuria ALAT > 2 x normal value Severe cardiac insufficiency in treatment with medicine which cannot be paused for 12 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vago<br>Truncally vagotomized subjects (due to duodenal ulcer operation) | Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor<br>* One tablet (50 mg)of DPP4 inhibitor is to be taken 12 and 1 hours before start of the oral glucose tolerance test (50 g glucose and 1.5 g paracetamol dissolved in 300 ml water)on day 3<br>* Other names: Galvus;Other: oral glucose<br>* 50 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.<br>* Other names: panodil;|
| Experimental: Cardia<br>Truncally vagotomized subjects (due to cardia resection) | Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor<br>* One tablet (50 mg)of DPP4 inhibitor is to be taken 12 and 1 hours before start of the oral glucose tolerance test (50 g glucose and 1.5 g paracetamol dissolved in 300 ml water)on day 3<br>* Other names: Galvus;Other: oral glucose<br>* 50 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.<br>* Other names: panodil;|
| Experimental: Ctrl<br>Healthy matched control subjects | Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor<br>* One tablet (50 mg)of DPP4 inhibitor is to be taken 12 and 1 hours before start of the oral glucose tolerance test (50 g glucose and 1.5 g paracetamol dissolved in 300 ml water)on day 3<br>* Other names: Galvus;Other: oral glucose<br>* 50 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.<br>* Other names: panodil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin secretion | The insulin secretion during a four-hour oral glucose tolerance test (OGTT) and an intravenous isoglycaemic clamp is evaluated | four hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma GLP-1 | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour | 12 time points within four hours | 
| plasma GIP | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour | 12 time points within four hours | 
| plasma glucagon | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour | 12 time points within four hours | 
| plasma GLP-2 | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour | 12 time points within four hours | 
| plasma PYY | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour | 12 time points within four hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vagotomy, vagus, GLP-1, Insulin secretion