Page 88 - Human Bile Acid Metabolism: a Postprandial Perspective

Chapter 5
In this study, we investigated the postprandial BA response in plasma in relation to insulin, GLP-1, and FGF19 levels. First, we analyzed the effects of mixed meal tests after an overnight and a 40-h fast as model of insulin resistance, because BA metabolism is altered in various models of insulin resistance (5, 14, 47). We subsequently assessed the effects of oral administration of glycine-conjugated DCA (gDCA) on postprandial glucose, insulin, and GLP-1 levels in a second separate experiment.
Materials and methods
Subjects
We performed two experiments with different subjects. We recruited 9 lean young men in experiment 1 and 10 lean young men in experiment 2. Exclusion criteria were body mass index (BMI) > 25 kg/m2, history of gallstones or biliary surgery, use of medication, substance abuse (nicotine or drugs, alcohol >2 units/day), liver test abnormalities (aspartate aminotransferase, alanine aminotransferase, bilirubin, gamma-glutamyl transferase, alkaline phosphatase), or abnormal fasted levels of plasma glucose or insulin. Written informed consent was obtained from all subjects before the start of the study procedures, and the studies were approved by the Academic Medical Center (AMC) Medical Ethics Committee (Amsterdam, The Netherlands). The experiments were conducted in accordance with the principles of the Declaration of Helsinki (sixth revision, 2008). Experiment 1 was filed at the ethical committee under ABR number NL4083401812. Experiment 2 was prospectively registered at www. trialregister.nl (NTR5849).
Study Design
Both separate, but related, experiments were mono center and conducted on the Experimental and Clinical Research Unit of the AMC, Amsterdam, The Netherlands.
Experiment 1. Each subject (n = 9) had two mixed meal tests on separate study days in a randomly assigned crossover design. Prior to each study day, subjects were instructed to either consume their regular diet followed by an overnight fast leading up to the study day (14 h FAST) or remain fasted for a total of 40 h (40 h FAST).
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