Intact Liver Innervation and Glucose and Glucagon-like Peptide-1 (GLP-1) Induced Insulin Secretion

Study Overview
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Brief Summary
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The aim of the study is to investigate the significance of intact nerve supply to the liver for the glucagon-like peptide-1 (GLP-1) induced insulin secretion. The hypothesis is that the effects of GLP-1 is transmitted through the GLP-1 receptor and that these effects involve sensory afferent neurons, probably primarily parasympathetic.

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. The aim of this study is to investigate the significance of intact liver innervation for the GLP-1 induced insulin secretion in liver transplanted patients; kidney transplanted control patients matched for immunosuppressive treatment, age, gender and body weight; and ten control persons matched for age, gender and body weight. The insulin secretion will be evaluated from blood samples that will be analyzed for insulin and c-peptide.

Official Title
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The Significance of Intact Liver Innervation for the Glucose and GLP-1 Induced Insulin Secretion

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: dipeptidyl peptidase 4 (DPP4) inhibitor
* Other: oral glucose
* Other: intravenous 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

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: Liver transplanted<br>10 Liver transplanted patients | Drug: dipeptidyl peptidase 4 (DPP4) 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 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol<br>* Other names: Panodil;Other: intravenous glucose<br>* 1.5 g paracetamol dissolved in 50 ml water is to be ingested orally within the first 2 minutes. Intravenous glucose is supplied in an amount to match the plasma glucose during the oral glucose tolerance test<br>* Other names: Panodil;|
| Experimental: Kidney transplanted<br>10 kidney transplanted individuals | Drug: dipeptidyl peptidase 4 (DPP4) 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 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol<br>* Other names: Panodil;Other: intravenous glucose<br>* 1.5 g paracetamol dissolved in 50 ml water is to be ingested orally within the first 2 minutes. Intravenous glucose is supplied in an amount to match the plasma glucose during the oral glucose tolerance test<br>* Other names: Panodil;|
| Experimental: Healthy controls<br>10 healthy controls | Drug: dipeptidyl peptidase 4 (DPP4) 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 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol<br>* Other names: Panodil;Other: intravenous glucose<br>* 1.5 g paracetamol dissolved in 50 ml water is to be ingested orally within the first 2 minutes. Intravenous glucose is supplied in an amount to match the plasma glucose during the oral glucose tolerance test<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 glucose | 20 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour | 20 time points within four hours | 
| 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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liver transplantation, kidney transplanted, glucagon-like peptide-1, insulin secretion, vagotomy