The effects of kisspeptin on β‐cell function, serum metabolites and appetite in humans

  • Chioma Izzi‐Engbeaya
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Alexander N. Comninos
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Sophie A. Clarke
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Anne Jomard
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Lisa Yang
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Sophie Jones
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Ali Abbara
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Shakunthala Narayanaswamy
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Pei Chia Eng
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Deborah Papadopoulou
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Julia K. Prague
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Paul Bech
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Ian F. Godsland
    Section of Metabolic Medicine, Department of Medicine, Imperial College London St Mary's Hospital London UK
  • Paul Bassett
    Statsconsultancy Ltd Amersham UK
  • Caroline Sands
    The MRC‐NIHR National Phenome Centre and Imperial BRC Clinical Phenotyping Centre, Division of Computational, Systems and Digestive Medicine, Department of Surgery and Cancer London UK
  • Stephane Camuzeaux
    The MRC‐NIHR National Phenome Centre and Imperial BRC Clinical Phenotyping Centre, Division of Computational, Systems and Digestive Medicine, Department of Surgery and Cancer London UK
  • Maria Gomez‐Romero
    The MRC‐NIHR National Phenome Centre and Imperial BRC Clinical Phenotyping Centre, Division of Computational, Systems and Digestive Medicine, Department of Surgery and Cancer London UK
  • Jake T. M. Pearce
    The MRC‐NIHR National Phenome Centre and Imperial BRC Clinical Phenotyping Centre, Division of Computational, Systems and Digestive Medicine, Department of Surgery and Cancer London UK
  • Matthew R. Lewis
    The MRC‐NIHR National Phenome Centre and Imperial BRC Clinical Phenotyping Centre, Division of Computational, Systems and Digestive Medicine, Department of Surgery and Cancer London UK
  • Elaine Holmes
    The MRC‐NIHR National Phenome Centre and Imperial BRC Clinical Phenotyping Centre, Division of Computational, Systems and Digestive Medicine, Department of Surgery and Cancer London UK
  • Jeremy K. Nicholson
    The MRC‐NIHR National Phenome Centre and Imperial BRC Clinical Phenotyping Centre, Division of Computational, Systems and Digestive Medicine, Department of Surgery and Cancer London UK
  • Tricia Tan
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Risheka Ratnasabapathy
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Ming Hu
    Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Gaelle Carrat
    Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Lorenzo Piemonti
    Diabetes Research Institute (SR‐DRI), IRCCS San Raffaele Scientific Institute Milan Italy
  • Marco Bugliani
    Department of Clinical and Experimental Medicine, Islet Cell Laboratory University of Pisa Pisa Italy
  • Piero Marchetti
    Department of Clinical and Experimental Medicine, Islet Cell Laboratory University of Pisa Pisa Italy
  • Paul R. Johnson
    Nuffield Department of Surgical Sciences University of Oxford Oxford UK
  • Stephen J. Hughes
    Nuffield Department of Surgical Sciences University of Oxford Oxford UK
  • A. M. James Shapiro
    Clinical Islet Laboratory and Clinical Islet Transplant Program University of Alberta Edmonton Canada
  • Guy A. Rutter
    Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK
  • Waljit S. Dhillo
    Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London London UK

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<jats:sec><jats:title>Aims</jats:title><jats:p>To investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m<jats:sup>−2</jats:sup>), we compared the effects of 1 nmol kg<jats:sup>−1</jats:sup> h<jats:sup>−1</jats:sup> kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.</jats:p></jats:sec>

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