Hyperglycemia and the Extra-pancreatic Effect of Incretins
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.
Extra-pancreatic Incretin Effect
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Determining the Extra-pancreatic Effects of Incretin Hormones During Euglycemic and Hyperglycemic Pancreatic Clamps|
- Glucose metabolism [ Time Frame: up to 4 hours ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]An infusion of the stable isotope [D5]glycerol will be performed to assess glycerol kinetics.
- Endothelial function [ Time Frame: Baseline, 2 hours, and 4 hours ] [ Designated as safety issue: No ]Ultrasound Doppler will be used to examine lower and upper limb blood flow and flow-mediated dilation
- Signaling [ Time Frame: Baseline, 2 hours, and 4 hours ] [ Designated as safety issue: No ]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.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Saline will be coninfused during the pancreatic clamp
GIP will be infused intravenously during the pancreatic clamp at 1.5 pmol/kg/min
GLP-1 will be infused intravenously during the pancreatic clamp at 0.5 pmol/kg/min
|Contact: Thomas PJ Solomon, PhDfirstname.lastname@example.org|
|Copenhagen, Capital Region, Denmark, 2100|
|Contact: Thomas PJ Solomon, PhD +4535457629 email@example.com|
|Principal Investigator: Thomas PJ Solomon, PhD|
|Sub-Investigator: Kristian Karstoft, MD|
|Principal Investigator:||Thomas PJ Solomon, PhD||Rigshospitalet, Denmark|