The Effect of GIP, GLP-1 and GLP-2 in Individuals With Genetically Altered Receptor Function

Participants with mutations in their GLP-1- and GIP receptor will attend five randomized experimental days, A1, A2, B, C and D. On day A1 an oral glucose tolerance test (OGTT) will be performed, and on day A2, an intravenous isoglycaemic glucose infusion (IIGI) will be performed. On experimental day B and C, the study participants will receive GLP-1 and GIP hormones, respectively, under stable glucose infusions and on experimental day D, they will receive infusion of salt water (placebo) under stable glucose infusion.

Participants with mutations in their GLP-2 receptor will attend three randomized experimental days, E, F and G. A mixed meal test (MMT) will be performed on day E, an infusion with GLP-2 during fasting blood glucose levels will be performed on day F, and infusion with salt water (placebo) during fasting blood glucose levels will be performed on day G.

Additionally, a DXA scan and arginine test will be performed on all study participants.

Inclusion criteria

• BMI 19-35 kg/m2

Exclusion criteria

• Treatment with medication or supplements that can not be discontinued for 12 hours
• >10 objects of alcohol weekly or abuse of narcotics
• Liver disease (defined as ALAT and/or ASAT ≥ 2 x normal levels)
• Decreased kidney function (creatine levels over reference interval)
• Uncontrollable increased blood pressure (> 140/90 mmHg)
• Low blood percentage (hemoglobin < 8.3 mmol/l)
• Special diet or planned weight change during trial period
• Other conditions that could be expected to affect the primary or secondary outcomes