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

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

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.

Study Overview

• Status: Unknown
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: dipeptidyl peptidase 4 (DPP4) inhibitor; Other: oral glucose; Other: intravenous glucose

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Astrid Plamboeck, M.D.; Phone Number: +45 26208174; Email: astridp@sund.ku.dk

Study Locations

• Denmark
  • Copenhagen
    • Hellerup, Copenhagen, Denmark, 2900
      • Recruiting
      • Department of Internal Medicine F' laboratory
      • Contact: Astrid Plamboeck, M.D.; Phone Number: +45 26208174; Email: astridp@sund.ku.dk
      • Contact: Tina Vilsbøll, M.D.; Phone Number: +45 39772461; Email: tivi@geh.regionh.dk
      • Principal Investigator: Astrid Plamboeck, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liver transplanted; 10 Liver transplanted patients	Drug: dipeptidyl 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; Other Names: Galvus; Other: oral glucose; 50 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol; Other Names: Panodil; Other: intravenous 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; Other Names: Panodil
Experimental: Kidney transplanted; 10 kidney transplanted individuals	Drug: dipeptidyl 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; Other Names: Galvus; Other: oral glucose; 50 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol; Other Names: Panodil; Other: intravenous 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; Other Names: Panodil
Experimental: Healthy controls; 10 healthy controls	Drug: dipeptidyl 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; Other Names: Galvus; Other: oral glucose; 50 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol; Other Names: Panodil; Other: intravenous 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; Other Names: Panodil

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: University of Copenhagen

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Anticipated): August 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: August 5, 2010
• First Submitted That Met QC Criteria: August 5, 2010
• First Posted (Estimate): August 6, 2010

Study Record Updates

• Last Update Posted (Estimate): January 6, 2012
• Last Update Submitted That Met QC Criteria: January 5, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: liver transplantation; insulin secretion; kidney transplanted; glucagon-like peptide-1; vagotomy
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: Transplant isoglycemia (AP)