Liver-enriched Antimicrobial Peptide 2

A Leap to Understand Glucoregulatory Effects of Liver-enriched Antimicrobial Peptide 2 (LEAP-2)

The investigators aim to investigate the physiological importance of LEAP-2 in healthy volunteers focusing on its potential insulinotropic effects.

The dramatic and almost immediate effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes (T2D) can only in part be explained by alterations in the plasma concentrations of known peptides. Thus, other - yet unknown - signals or hormones elicited from the endocrine cells of the small intestine may play an important role for the remission of T2D observed following RYGB. In a recent study, a predicted sequence of liver-enriched antimicrobial peptide 2 (LEAP-2) was shown to induce a glucose-stimulated insulin secretion in isolated human pancreatic islets. The fragment was subsequently identified to be circulating in human plasma in concentrations comparable to the circulating levels of other known gut secreted hormones, hereby validating that LEAP-2 is an endogenous circulating peptide.

The investigators hypothesise that LEAP-2 increases insulin secretion during a graded glucose infusion as assessed by plasma insulin and C-peptide compared with saline (placebo) in healthy subjects. The study is designed as a clinical, placebo-controlled, double-blinded cross-over study involving two experimental study days and ten young healthy male participants. The co-primary endpoints are the difference in plasma insulin levels during a graded glucose infusion and beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration between the two study days with either saline (placebo) or LEAP-2 infusion.

Inclusion Criteria:

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

Exclusion Criteria:

• Anaemia (haemoglobin below normal range)
• ALAT and/or ASAT >2 times normal values or history of hepatobiliary and/or gastrointestinal disorder(s)
• Nephropathy (serum creatinine above normal range and/or albuminuria)
• Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses
• Any ongoing medication that the investigator evaluates would interfere with trial participation.
• First- and second-degree relatives with diabetes
• Regular tobacco smoking