Liver Transplantation
Conditions
Keywords
liver transplantation, kidney transplanted, glucagon-like peptide-1, insulin secretion, vagotomy
Brief summary
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
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.
Interventions
DRUGdipeptidyl peptidase 4 (DPP4) inhibitor
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
OTHERoral glucose
50 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol
OTHERintravenous glucose
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
Sponsors
University of Copenhagen
University Hospital, Gentofte, Copenhagen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| insulin secretion | four hours | The insulin secretion during a four-hour oral glucose tolerance test (OGTT) and an intravenous isoglycaemic clamp is evaluated |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| plasma GLP-1 | 12 time points within four hours | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour |
| plasma GIP | 12 time points within four hours | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour |
| plasma glucose | 20 time points within four hours | 20 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour |
| plasma GLP-2 | 12 time points within four hours | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour. |
| plasma PYY | 12 time points within four hours | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour |
| plasma glucagon | 12 time points within four hours | 12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour |
Countries
Denmark
Contacts
Primary ContactAstrid Plamboeck, M.D.
Outcome results
None listed