LEAP2 on Postprandial Glucose Metabolism and Food Intake

University Hospital, Gentofte, Copenhagen

Status and phase

Completed

Early Phase 1

Conditions

Obesity

Treatments

Biological: Liver-enriched antimicrobial peptide 2

Biological: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT04621409

LEAP2

Details and patient eligibility

About

The study aim to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in healthy volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in healthy subjects.

Full description

In a recent study, the molecular phenotype of enteroendocrine cells in the small intestine before and after Roux-en-Y Gastric Bypass (RYGB) surgery in obese individuals was examined. Enteroendocrine cells were identified and isolated from intestinal biopsies and analysed for differentially expressed genes by Illumina High Throughput RNA-sequencing. It was discovered that the gene encoding liver-enriched antimicrobial peptide 2 (LEAP-2), a naturally occurring peptide in humans, was significantly upregulated compared to baseline expression. Interestingly, LEAP-2 was recently shown to antagonize ghrelin function in response to feeding in mice. Moreover, the mature murine LEAP-2 peptide is identical in mice and humans. Thus, LEAP-2 has been identified as an endogenous peptide that may be able to alter feeding behaviour and maintenance of glucose levels during calorie restriction.

The study hypothesis is that LEAP-2 alters postprandial glucose metabolism and decreases appetite as well as food intake in relation to a liquid mixed meal and a standardised ad libitum meal compared with saline (placebo) in healthy subjects.

Enrollment

20 patients

Sex

Male

Ages

18 to 25 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Caucasian men
Age between 18 and 25 years
Body mass index between 20-35 kg/m2
Informed consent

Exclusion criteria

Anaemia (haemoglobin below normal range)
Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary and/or gastrointestinal disorder(s)
Nephropathy (serum creatinine above normal range and/or albuminuria)
Allergy or intolerance to ingredients included in the standardised meals
First-degree relatives with diabetes and/or glycated haemoglobin (HbA1c) >48 mmol/mol
Regular tobacco smoking or use of other nicotine-containing products
Any ongoing medication that the investigator evaluates would interfere with trial participation.
Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses