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

University Hospital, Gentofte, Copenhagen10 enrolled

Overview

Infusion of glucagon-like peptide 2 (GLP-2) during euglycaemia, hypoglycaemia and hyperglycaemia and evaluation of the effect on glucagon secretion in healthy subjects.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Glucose Metabolism Disorders Endocrine or Metabolic Disease

Interventions

Glucagon-like peptide 2OTHER

Human glucagon-like peptide 2

SalineOTHER

Placebo

GlucoseOTHER

20% (w/v) glucose infusion for regulating plasma glucose

Insulin

Eligibility

Sex: MALEMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Center for Clinical Metabolic Research

Hellerup, Copenhagen, Denmark

Outcomes

Primary Outcomes

Glucagon secretion

Assessed by difference in absolute plasma glucagon concentrations (measured in pmol/liter) and incremental (baseline-subtracted) area under curve (AUC) for plasma glucagon

Time frame: 110 minutes

Secondary Outcomes

Plasma glucose

Measured in mmol/liter

Time frame: 110 minutes

GLP-1

Glucagon-like peptide 1, Measured in pmol/liter

Time frame: 110 minutes

GLP-2

Glucagon-like peptide 2, Measured in pmol/liter

Time frame: 110 minutes

Insulin

Measured in pmol/liter

Time frame: 110 minutes

GIP

Glucose dependent insulinotropic hormone, Measured in pmol/liter

Time frame: 110 minutes

OXM

Oxytomodulin, Measured in pmol/liter

Time frame: 110 minutes

Amino acids

Measured in pmol/liter

Time frame: 110 minutes

CCK

Cholecystokinin, Measured in pmol/liter

Time frame: 110 minutes

Gastrin

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.