GLP-1 Signaling in Truncally Vagotomized Subjects

Study Overview
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Brief Summary
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Investigation of the importance of vagal signaling for the glucohomeostatic effects of GLP-1. The study will include physiological studies of truncally vagotomized participants and matched controls.

Official Title
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Vagal Mechanisms Mediating the Effects of Glucagon-Like Peptide 1 (GLP-1) on the Endocrine Pancreas - the Entero-endocrine Axis.

Conditions
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Physiology

Intervention / Treatment
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* Drug: Tablet Sitagliptin 100mg (evening before and morning of experiments)
* Other: Intestinal Fructose administration


Participation Criteria
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Eligibility Criteria
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Truncally vagotomized individuals: Inclusion Criteria: Normal fasting plasma glucose Normal haemoglobin concentration Cardiaresection with a pyloroplasty Informed consent Exclusion Criteria: Diabetes mellitus Disposition for diabetes mellitus Intestinal disease (apart from cardia resection+pyloroplasty) Disposition of inflammatory bowel disease Intestinal resection (apart from cardia resection+pyloroplasty) Body mass index (BMI) > 27,5 kg/m2 Tobacco use Nephropathy (se-creatinine> 130 µM and/or albuminuria) Liver disease (ALAT and/or ASAT >2 × refference value) known heart condition medicinal use, that may not be paused for 12 hours Obstipation swallowing difficulties previous problems with intestinal tube placement Latex allergy Fructose malabsorption Known diseases in the pharynx Previous facial or cranial fractures Sinusitis Bleeding diathesis Matched controls: Inclusion Criteria: Normal fasting plasma glucose Normal haemoglobin concentration Informed consent Exclusion Criteria: Cardiaresection with a pyloroplasty Diabetes mellitus Disposition for diabetes mellitus Intestinal disease (apart from cardia resection+pyloroplasty) Disposition of inflammatory bowel disease Intestinal resection tarmresektion (apart from cardia resection+pyloroplasty) Body mass index (BMI) > 27,5 kg/m2 Tobacco use Nephropathy (se-creatinine> 130 µM and/or albuminuria) Liver disease (ALAT and/or ASAT >2 × refference value) known heart condition medicinal use, that may not be paused for 12 hours Obstipation swallowing difficulties previous problems with intestinal tube placement Latex allergy Fructose malabsorption Known diseases in the pharynx Previous facial or cranial fractures Sinusitis Bleeding diathesis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enteral fructose with DPP-4 inhibition<br>Enteral fructose + DPP-4 inhibition (sitagliptin) After DPP4 inhibition using Tablet Sitagliptin 100mg on the evening before and on the morning of experimentation enteral fructose is given via an intestinal tube (intrajejunal) to either truncally vagotomised and control individuals. | Drug: Tablet Sitagliptin 100mg (evening before and morning of experiments)<br>* On one of two experiment days participants will have Dipeptidyl peptidase 4 activity inhibited using a DPP-4 inhibitor (Sitagliptin).<br>Other: Intestinal Fructose administration<br>* On both experimental days fructose (35g dissolved in water, total volume 100mL) will be administered via an intrajejunal tube<br>|
| Experimental: Enteral fructose without DPP-4 inhibition<br>Enteral fructose without DPP-4 inhibition (sitagliptin) After DPP4 inhibition using Tablet Sitagliptin 100mg on the evening before and on the morning of experimentation enteral fructose is given via an intestinal tube (intrajejunal) to either truncally vagotomised and control individuals. | Other: Intestinal Fructose administration<br>* On both experimental days fructose (35g dissolved in water, total volume 100mL) will be administered via an intrajejunal tube<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion | Evaluated by c-peptide and insulin levels - Plasma collected up to 4 hours will be analyzed for peptide hormones | up to 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon secretion | Plasma collected over 4 hours will be analyzed for peptide hormones | 4 hours | 
| Glucose levels | Plasma collected over 4 hours will be analyzed for glucose | 4 hours | 
| Pancreatic Polypeptide levels | Plasma collected over 4 hours will be analyzed for peptide hormones | 4 hours | 
| GIP secretion | Plasma collected over 4 hours will be analyzed for peptide hormones | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physiology