Intact Vagal Innervation for and Glucagon-like Peptide-1 (GLP-1) Effects

The Significances of Intact Vagal Innervation for the Glucose and GLP1 Induced Insulin Secretion

The aim of this study is to investigate the role of transmission via the vagal nerve for the effect of glucose and Glucagon-like peptide-1 (GLP-1) in respect to insulin secretion.

The hypothesis is that a great deal of the effects of GLP-1 is mediated via the nervous system and for this reason the investigators will research individuals with and without intact nervous supply.

Study Overview

• Status: Unknown
• Conditions: Vagotomy, Truncal
• Intervention / Treatment: Drug: Dipeptidyl peptidase 4 (DPP 4) inhibitor; Other: oral 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. We investigated the role of intact vagal innervations on the effect of glucose and GLP-1 on the insulin secretion

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

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Hellerup, Copenhagen, Denmark, 2900
      • Department of internal medicine F´laboratory, Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• 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: Vago; Truncally vagotomized subjects (due to duodenal ulcer operation)	Drug: Dipeptidyl peptidase 4 (DPP 4) 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 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.; Other Names: panodil
Experimental: Cardia; Truncally vagotomized subjects (due to cardia resection)	Drug: Dipeptidyl peptidase 4 (DPP 4) 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 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.; Other Names: panodil
Experimental: Ctrl; Healthy matched control subjects	Drug: Dipeptidyl peptidase 4 (DPP 4) 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 g glucose dissolved in 300 ml water with 1,5 g paracetamol is to be ingested orally within the first 15 minutes.; 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 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 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
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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: University of Copenhagen
• Investigators: Principal Investigator: Astrid Plamboeck, MD, University Hospital, Gentofte, Copenhagen; Study Director: Tina Vilsbøll, MD, dr.med, University Hospital, Gentofte, Copenhagen

Publications and helpful links

General Publications

• Plamboeck A, Veedfald S, Deacon CF, Hartmann B, Wettergren A, Svendsen LB, Meisner S, Hovendal C, Knop FK, Vilsboll T, Holst JJ. Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty. Eur J Endocrinol. 2013 Jul 6;169(2):187-201. doi: 10.1530/EJE-13-0264. Print 2013 Aug.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): October 1, 2011
• 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): December 7, 2012
• Last Update Submitted That Met QC Criteria: December 6, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: GLP-1; vagotomy; Insulin secretion; vagus
• 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: Truncated isoglycemia