Hyperglycemia and the Extra-pancreatic Effect of Incretins

December 2, 2014 updated by: Thomas Solomon, Rigshospitalet, Denmark

Determining the Extra-pancreatic Effects of Incretin Hormones During Euglycemic and Hyperglycemic Pancreatic Clamps

Incretin hormones (GLP-1 and GIP) released from the intestine in response to meal ingestion augment insulin secretion from the pancreas to help maintain glycemic control. Studies in vitro and in vivo have shown that these incretin hormones also have functional effects in other tissues independent of the insulin secretory response. Both GLP-1 and GIP stimulate insulin secretion in a glucose-dependent manner, however the glucose-dependency of their extra-pancreatic effects has not been examined in vivo. By using pancreatic clamp methodology during euglycemic and hyperglycemic conditions we will test the hypothesis that extra-pancreatic effects of GLP-1 and GIP are glucose-dependent.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Capital Region
      • Copenhagen, Capital Region, Denmark, 2100
        • Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • age 18-60 years
  • BMI 18-30 kg/m2
  • Male
  • Normal glycemic control (fasting glucose <5.6 mM)

Exclusion Criteria:

  • Evidence of chronic disease
  • Smoking
  • Active weight loss (>2 kg in previous 6 months)
  • Treatment with drugs known to affect our outcome varaibles

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Control
Saline will be coninfused during the pancreatic clamp
Biological: Saline
Experimental: GIP
GIP will be infused intravenously during the pancreatic clamp at 1.5 pmol/kg/min
Biological: GIP
Experimental: GLP-1
GLP-1 will be infused intravenously during the pancreatic clamp at 0.5 pmol/kg/min
Biological: GLP-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose metabolism
Time Frame: up to 4 hours
Pancreatic clamp will be performed including infusion of somatostatin and replacement of basal insulin, glucagon, and growth hormone. During pancreatic clamps, euglycemia (5 mM) will be maintained via exogenous glucose infusion for the first 2-hours, followed by hyperglycemia (+5 mM) for the final 2-hours. An infusion of the stable isotope [U13C]glucose will be performed to assess glucose kinetics. Expired air will be collected for the analysis of [U13C]glucose into 13CO2.
up to 4 hours
Lipid metabolism
Time Frame: up to 4 hours
An infusion of the stable isotope [D5]glycerol will be performed to assess glycerol kinetics.
up to 4 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial function
Time Frame: Baseline, 2 hours, and 4 hours
Ultrasound Doppler will be used to examine lower and upper limb blood flow and flow-mediated dilation
Baseline, 2 hours, and 4 hours
Signaling
Time Frame: Baseline, 2 hours, and 4 hours
Skeletal muscle (vastus lateralis) and subcutaneous abdominal adipose biopsies will be obtained under local anaesthetic by the Bergstrom needle technique. Intracellular signalling related to glucose and lipid metabolism will be measured.
Baseline, 2 hours, and 4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Investigators

  • Principal Investigator: Thomas PJ Solomon, PhD, Rigshospitalet, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

December 11, 2012

First Submitted That Met QC Criteria

December 12, 2012

First Posted (Estimate)

December 13, 2012

Study Record Updates

Last Update Posted (Estimate)

December 3, 2014

Last Update Submitted That Met QC Criteria

December 2, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Other Study ID Numbers

  • PancClamp

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Extra-pancreatic Incretin Effect

Clinical Trials on Saline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Serbia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe