Determining the Extra-pancreatic Effects of Incretin Hormones During Euglycemic and Hyperglycemic Pancreatic Clamps
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Rigshospitalet, Denmark
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Glucose metabolism
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •age 18-60 years
- •BMI 18-30 kg/m2
- •Normal glycemic control (fasting glucose <5.6 mM)
Exclusion Criteria
- •Evidence of chronic disease
- •Active weight loss (>2 kg in previous 6 months)
- •Treatment with drugs known to affect our outcome varaibles
Arms & Interventions
Control
Saline will be coninfused during the pancreatic clamp
Intervention: Saline (Biological)
GIP
GIP will be infused intravenously during the pancreatic clamp at 1.5 pmol/kg/min
Intervention: GIP (Biological)
GLP-1
GLP-1 will be infused intravenously during the pancreatic clamp at 0.5 pmol/kg/min
Intervention: GLP-1 (Biological)
Outcomes
Primary Outcomes
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.
Lipid metabolism
Time Frame: up to 4 hours
An infusion of the stable isotope \[D5\]glycerol will be performed to assess glycerol kinetics.
Secondary Outcomes
- Endothelial function(Baseline, 2 hours, and 4 hours)
- Signaling(Baseline, 2 hours, and 4 hours)
Investigators
Thomas Solomon
Senior Researcher
Rigshospitalet, Denmark