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

Not Applicable

• Conditions: Liver Transplantation
• Interventions: Drug: dipeptidyl peptidase 4 (DPP4) inhibitor; Other: oral glucose; Other: intravenous glucose

• Registration Number: NCT01176708
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

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.

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2010-08-05
• Study First Submitted QC: 2010-08-05
• Study First Posted: 2010-08-06
• Status Verified: 2012-01
• Last Update Submitted: 2012-01-05
• Last Update Posted: 2012-01-06
• Primary Completion: 2012-08
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Liver transplanted	dipeptidyl peptidase 4 (DPP4) inhibitor	10 Liver transplanted patients
Liver transplanted	oral glucose	10 Liver transplanted patients
Liver transplanted	intravenous glucose	10 Liver transplanted patients
Kidney transplanted	dipeptidyl peptidase 4 (DPP4) inhibitor	10 kidney transplanted individuals
Kidney transplanted	oral glucose	10 kidney transplanted individuals
Kidney transplanted	intravenous glucose	10 kidney transplanted individuals
Healthy controls	dipeptidyl peptidase 4 (DPP4) inhibitor	10 healthy controls
Healthy controls	oral glucose	10 healthy controls
Healthy controls	intravenous glucose	10 healthy controls

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
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-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 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

Trial Locations

Locations (1)

Department of Internal Medicine F' laboratory; 🇩🇰 Hellerup, Copenhagen, Denmark