The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis.
The investigators hypothesize that even modest increments in endogenous GLP-1 secretion will elicit important antidiabetic effects of GLP-1. To evaluate whether bile acids have such effects, the investigators plan to perform intraduodenal infusion of two different bile acids and placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
20
Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
100 ml saline
Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen
Hellerup, Copenhagen, Denmark
Change in GLP-1
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in insulin
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in C-peptide
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucagon-like-peptide 2 (GLP-2)
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in glucose-dependent insulinotropic polypeptide (GIP)
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in peptide YY (PYY)
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in oxyntomodulin
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in bile acids
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in gastrin
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
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Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0.
Change in CCK
Time frame: At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes
Change in appetite, satiety and prospective food consumption
Evaluated by Visual Analog Scale (VAS)
Time frame: At baseline, and 30, 60, 90, 120 and 180 minutes
Change in gallbladder volume
Evaluated by ultrasound
Time frame: -30, 0 (baseline), 30, 60, 120 og 180 minutes
Change in basal metabolic rate
Evaluated by indirect calorimetry
Time frame: At -30, 60 og 150 minutes
Change in bile acid composition
Evaluated by duodenal aspiration
Time frame: At -30, 0, 30, 60, 120 og 180 minutes