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

University Hospital, Gentofte, Copenhagen30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Liver Transplantation

Interventions

dipeptidyl peptidase 4 (DPP4) inhibitorDRUG

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

oral glucoseOTHER

50 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol

intravenous glucoseOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Department of Internal Medicine F' laboratory

Hellerup, Copenhagen, Denmark

RECRUITING

Outcomes

Primary Outcomes

insulin secretion

The insulin secretion during a four-hour oral glucose tolerance test (OGTT) and an intravenous isoglycaemic clamp is evaluated

Time frame: four hours

Secondary Outcomes

plasma glucose

20 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour

Time frame: 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