GA-18: The Role of Endogenous GIP in Glycosis Metabolism During Fasting
Phase: EARLY_PHASE1
Conditions: Obesity
Sponsor: Frederikke Koefoed-Hansen

ID: H-22063621 
Protocol GA-18 
Title: The role of endogenous GIP in glucose metabolism during fasting 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ID: H-22063621 
Date: 10/04/2024 

ID: H-22063621 
Introduction 
The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is secreted is secreted 
from enteroendocrine K cells in the small intestine following food. GIP have a powerful effect on 
glucose-induced insulin secretion from pancreatic beta cells, the incretin effect. GIP accounts for 
about 45 % of insulin secretion after food intake. Exogenous GIP during fasting stimulates glucagon 
secretion in low blood glucose and has an anabolic effect in/on fat and bone metabolism in healthy 
individuals. However, we do not fully understand the physiological role of GIP and with this study, 
we will investigate how endogenous GIP affects the body during fasting.  
 
Purpose  
The purpose of this project is to investigate the effects of endogenous GIP in healthy, obese 
individuals. With the infusion of the GIP receptor antagonist (GIP(3-30)NH2) is it possible to 
describe the effects of endogenous GIP, by comparing with what happens during a saline infusion 
(placebo)  
 
Hypothesis  
We hypothesize that endogenous GIP has physiological effects in fasting and that we will see a 
decrease in glucagon levels during GIP(3-30)NH2 infusion compared to placebo.  
 
Study design  
In a randomized, placebo-controlled, double-blind, crossover design comprising two experimental 
days, 12 participants will receive 180-minute infusions of GIP(3-30)NH2 (800 pmol/kg/min) and 
placebo (saline) in a randomized order respectively, after observed 10 hours fast. An ad libitum 
meal be serves at time 180 min, during continuous infusion. To keep the infusate content hidden for 
the investigator and the participants, the preparation of the infusate during the experimental days 
will be handled by an employee otherwise not involved in the study. During the trial, the participant 
assesses and records current appetite and thirst on standardized VAS forms. Blood pressure and 
heart rate are measured at time: -30 min, 0 min, 30 min, 60 min, 90 min, 120 min, 150 min and 180 
min. Blood samples (0,2 ml) are taken at time: -30 min, -20 min, 0 min, 15 min, 30 min, 60 min, 90 
min, 120 min, 150 min and 180 min. Brown adipose tissue activity is measured with thermal 
camera, and resting metabolic rate is determined with indirect calorimetry.  
 
Calculations and statistics  
Data will be processed and presented using standard descriptive statistics. Baseline-substracted and 
absolute values for AUC will be calculated using numerical integration. The GIP(3-30)NH2 effect is 
calculated for a given endpoint as a percentage of the placebo infusion: Effect = 100 – (GIP(3-
30)NH2 / placebo)