Understanding Individual Variability in Neuronal Signal Transmission to Target Organs in Health and Disease

Overview

The goal of this clinical trial is to evaluate the influence of parasympathetic transmission from the brain to different metabolic organs. This transmission can be blocked with the muscarinic antagonist atropine. Participants will undergo an oral glucose tolerance test combined with a double tracer dilution technique either with atropine infusion or placebo. Healthy individuals and high-risk individuals will be compared to identify possible changes in signaling in high-risk groups. In addition, men and women will be included to take into account possible sex differences.

This research project aims to investigate to what extent the parasympathetic nervous system is responsible for the transmission of signals from the brain to peripheral organs. Furthermore, the study will investigate sex differences and differences between healthy and high-risk individuals on brain-derived coordination of postprandial signaling for metabolic control. Therefore, parasympathetic blockade will be introduced by atropine infusion (on one day) versus saline infusion as placebo (on another day) in a randomized fashion. For safety reasons, only the participants will be blinded. Infusion will start 20 minutes before a 75 gram oral glucose tolerance test (oGTT) and last until the end of the 2h oGTT. The oGTT will introduce a postprandial state. Additionally, 1000 mg Paracetamol will be added to the solution to study gastric emptying. This approach will be combined with a double-tracer dilution technique. Labeled glucose (\[6,6-2H\]glucose) will be infused 120 minutes before and during the oGTT (120 min) and will be used to address endogenous glucose production. The glucose drink from the oGTT will be enriched with \[U-13C6\]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd).