Glucagon-like Peptide 2 - a Glucose Dependent Glucagonotropic Hormone?

This is a cross-over, randomized, double-blinded study in which 10 participants will undergo 6 experimental days each. The participants will have their plasma glucose clamped at either euglycaemia (fasting level), hypoglycemia (2,5 mmol/l) or hyperglycemia (10 mmol/l) during infusion of GLP-2 or saline (placebo)

The six days will be as follows:

• Euglycaemia + Placebo
• Euglycaemia + GLP-2
• Hyperglycaemia + Placebo
• Hyperglycaemia + GLP-2
• Hypoglycaemia + Placebo
• Hypoglycaemia + GLP-2

The primary endpoint will be levels of plasma glucagon. Secondary endpoint will be levels of GLP-1, GLP-2, Insulin/C-peptide, OXM, Amino acids, CCK, Gastrin, norepinephrine, bile acids, FGF-19/FGF-21. Secondary endpoints will also include ultrasound scan of the gallbladder.

Inclusion criteria

• Caucasian ethnicity
• Body mass index (BMI): 18.5-27 kg/m2
• Glycated haemoglobin (HbA1c) < 42 mmol/mol
• Normal haemoglobin (8.3-10.5 mmol/l)
• Informed and oral and written consent

Exclusion criteria

• Prediabetes, type 1 diabetes or type 2 diabetes or first-degree relatives with type 1 or type 2 diabetes
• Nephropathy (eGFR < 60 and/or albuminuria)
• Known liver disease and/or alanine transaminase (ALAT) or aspartate transaminase (ASAT) > 2 × upper normal limit
• Bilirubin > 25 μmol/l
• Known intestinal disease or previous surgery of the intestines
• Active or recent malignant disease
• Treatment with medicine that cannot be paused for 12 hours
• Any condition considered incompatible with participation by the investigators