LEAP2 on Postprandial Glucose Metabolism and Food Intake
- Conditions
- Obesity
- Interventions
- Biological: Liver-enriched antimicrobial peptide 2Biological: Placebo
- Registration Number
- NCT04621409
- Lead Sponsor
- University Hospital, Gentofte, Copenhagen
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 20
- Caucasian men
- Age between 18 and 25 years
- Body mass index between 20-35 kg/m2
- Informed consent
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description liver-enriched antimicrobial peptide 2 Liver-enriched antimicrobial peptide 2 IV infusion of LEAP2, approximately 5 hours Placebo Placebo IV infusion of saline, approximately 5 hours
- Primary Outcome Measures
Name Time Method Food intake 260 to 290 minutes Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules (kJ) and kJ/kg body weight of food eaten during the ad libitum meal.
- Secondary Outcome Measures
Name Time Method VAS -30 to 290 minutes Visual analogue scales (VASs) assessing appetite, satiety and hunger sensations (from 0 to 10 cm on a scale = from mimimum to maximum sensation)
Alterations in gastric emptying -30 to 290 minutes Paracetamol concentration in plasma after intake of 1.5 g paracetamol
Changes in resting energy expenditure (REE) -30 to 290 minutes Changes in resting energy expenditure (REE) measured by indirect calorimetry
Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration -30 to 290 minutes Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration
Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones -30 to 290 minutes Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones
Assessment of nitrogen balance and protein breakdown in urine -30 to 290 minutes Urine concentrations of urea for assessment of nitrogen balance and protein breakdown
Triglyceride responses -30 to 290 minutes Plasma triglyceride
Cholesterol responses -30 to 290 minutes Plasma cholesterol
Free fatty acid responses -30 to 290 minutes Plasma free fatty acid
Trial Locations
- Locations (1)
Center for Clinical Metabolic Research
🇩🇰Hellerup, Denmark