LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men

Christoffer A Hagemann, Malene S Jensen, Stephanie Holm, Lærke S Gasbjerg, Sarah Byberg, Kirsa Skov-Jeppesen, Bolette Hartmann, Jens J Holst, Flemming Dela, Tina Vilsbøll, Mikkel B Christensen, Birgitte Holst, Filip K Knop


The gastric hormone ghrelin stimulates food intake and increases plasma glucose through activation of the growth hormone secretagogue receptor (GHSR). Liver-expressed antimicrobial peptide 2 (LEAP2) has been proposed to inhibit actions of ghrelin through inverse effects on GHSR activity. Here, we investigate the effects of exogenous LEAP2 on postprandial glucose metabolism and ad libitum food intake in a randomized, double-blind, placebo-controlled, crossover trial of 20 healthy men. We report that LEAP2 infusion lowers postprandial plasma glucose and growth hormone concentrations and decreases food intake during an ad libitum meal test. In wild-type mice, plasma glucose and food intake are reduced by LEAP2 dosing, but not in GHSR-null mice, pointing to GHSR as a potential mediator of LEAP2's glucoregulatory and appetite-suppressing effects in mice.

Original languageEnglish
Article number100582
JournalCell reports. Medicine
Issue number4
Pages (from-to)100582
Publication statusPublished - 19 Apr 2022


  • Animals
  • Blood Glucose
  • Eating
  • Ghrelin
  • Glucose/pharmacology
  • Humans
  • Mice
  • Receptors, Ghrelin


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