Hyperglycemia and the Extra-pancreatic Effect of Incretins

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01749163
Recruitment Status : Completed
First Posted : December 13, 2012
Last Update Posted : December 3, 2014
Information provided by (Responsible Party):
Thomas Solomon, Rigshospitalet, Denmark

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Extra-pancreatic Incretin Effect Glucose Effectiveness Biological: Saline Biological: GIP Biological: GLP-1 Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Determining the Extra-pancreatic Effects of Incretin Hormones During Euglycemic and Hyperglycemic Pancreatic Clamps
Study Start Date : September 2012
Actual Primary Completion Date : December 2013
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones
U.S. FDA Resources

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

Primary Outcome Measures :
  1. 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.

  2. Lipid metabolism [ Time Frame: up to 4 hours ]
    An infusion of the stable isotope [D5]glycerol will be performed to assess glycerol kinetics.

Secondary Outcome Measures :
  1. 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

  2. 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.

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01749163

Copenhagen, Capital Region, Denmark, 2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Principal Investigator: Thomas PJ Solomon, PhD Rigshospitalet, Denmark

Responsible Party: Thomas Solomon, Senior Researcher, Rigshospitalet, Denmark Identifier: NCT01749163     History of Changes
Other Study ID Numbers: PancClamp
First Posted: December 13, 2012    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014

Additional relevant MeSH terms:
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs