Intact Vagal Innervation 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 Glucagon-like peptide-1 (GLP-1) in respect to gastric emptying, appetite and food intake. The hypothesis is that a great deal of the effects of GLP-1 is mediated via the nervous system and for this reason the researchers will investigate 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 GLP-1 on the food intake, gastric emptying (GE) and appetite.

Official Title
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The Significance of Intact Vagal Innervation for the GLP-1 Induced Inhibition of Gastric Emptying, Appetite and Food Intake

Conditions
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Vagotomy, Truncal

Intervention / Treatment
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* Drug: GLP-1
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: truncal vagotomy normal hemoglobin informed consent Age, gender and weight matched controls normal hemoglobin informed consent Exclusion Criteria: type 1 diabetes mellitus or type 2 diabetes mellitus body mass index > 30 kg/m2 inflammatory bowel disease intestinal resection nephropathy (serum creatinine > 150 µM and/or albuminuria) liver disease (ALAT and/or ASAT > 2 x normal value) treatment with medicine which cannot be paused for 12 hours

Ages Eligible for Study
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Minimum Age: 18 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: GLP-1<br>* 1.2 pmol/kg/min GLP-1 will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes. After four hours an ad libitum meal will be supplied<br>* Other names: Panodil;Other: Saline<br>* Saline (isotonic NaCl) will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes. After four hours an ad libitum meal will be supplied<br>* Other names: Panodil;|
| Experimental: Cardia<br>truncally vagotomized subjects (due to esophagus resection) | Drug: GLP-1<br>* 1.2 pmol/kg/min GLP-1 will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes. After four hours an ad libitum meal will be supplied<br>* Other names: Panodil;Other: Saline<br>* Saline (isotonic NaCl) will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes. After four hours an ad libitum meal will be supplied<br>* Other names: Panodil;|
| Experimental: Healthy controls<br>Healthy control subjects | Drug: GLP-1<br>* 1.2 pmol/kg/min GLP-1 will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes. After four hours an ad libitum meal will be supplied<br>* Other names: Panodil;Other: Saline<br>* Saline (isotonic NaCl) will be infused intravenously during the four hour meal test (100 g Ny NAN1 and 1.5 g paracetamol dissolved in 300 ml water) ingested over 10 minutes. After four hours an ad libitum meal will be supplied<br>* Other names: Panodil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying | Gastric emptying will be assessed using a liquid meal with 1.5 g paracetamol added and continuous blood sampling for measuring paracetamol concentration during four hours | four hours | 
| Appetite | Hunger, satiation, and fullness will be assessed before, during and after a liquid meal with 1.5 g paracetamol added using a visual analog scale (VAS) | four hours | 
| Food intake | After the liquid meal test, the volunteers will be offered a meal to assessed their ad libitum food intake | five hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma glucose |  | four hours | 
| serum insulin and c-peptide |  | four hours | 
| plasma glucagon |  | four hours | 
| plasma GLP-1 |  | four hours | 
| endogenous GLP-1 | endogenous GLP-1 will be assessed as plasma GLP-2 concentration | four hours | 
| plasma GIP |  | four hours | 
| serum paracetamol |  | four hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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truncal vagotomy, GLP-1, gastric emptying, appetite, food intake