PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context
Claudia Guida,
Sam D. Stephen,
Michael Watson,
Niall Dempster,
Pierre Larraufie,
Thomas Marjot,
Tamsin Cargill,
Lisa Rickers,
Michael Pavlides,
Jeremy Tomlinson,
Jeremy F.L. Cobbold,
Chun-Mei Zhao,
Duan Chen,
Fiona Gribble,
Frank Reimann,
Richard Gillies,
Bruno Sgromo,
Patrik Rorsman,
John D. Ryan,
Reshma D. Ramracheya
Affiliations
Claudia Guida
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
Sam D. Stephen
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
Michael Watson
Translational Gastroenterology Unit, University of Oxford, Oxford, UK
Niall Dempster
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
Pierre Larraufie
Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
Thomas Marjot
Translational Gastroenterology Unit, University of Oxford, Oxford, UK
Tamsin Cargill
Translational Gastroenterology Unit, University of Oxford, Oxford, UK
Lisa Rickers
Oxford Bariatric Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Michael Pavlides
Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, UK; Oxford NIHR Biomedical Research Centre, Oxford, UK
Jeremy Tomlinson
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
Jeremy F.L. Cobbold
Translational Gastroenterology Unit, University of Oxford, Oxford, UK
Chun-Mei Zhao
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
Duan Chen
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
Fiona Gribble
Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
Frank Reimann
Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
Richard Gillies
Oxford Bariatric Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Bruno Sgromo
Oxford Bariatric Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
Patrik Rorsman
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
John D. Ryan
Translational Gastroenterology Unit, University of Oxford, Oxford, UK; Correspondence to: J. D. Ryan, Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
Reshma D. Ramracheya
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK; Correspondence to: R. D. Ramracheya, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, OX3 7LE Oxford, UK.
Background: Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic islet secretory function and glucose metabolism remains under-studied. Methods: Changes in PYY concentrations were examined in obese patients after bariatric surgery and compared to healthy controls. Human pancreatic islet function was tested upon treatment with sera from patients before and after the surgery, in presence or absence of PYY. Alterations in intra-islet PYY release and insulin secretion were analysed after stimulation with short chain fatty acids (SCFAs), bile acids and the cytokine IL-22. Findings: We demonstrate that PYY is a key effector of the early recovery of impaired glucose-mediated insulin and glucagon secretion in bariatric surgery. We establish that the short chain fatty acid propionate and bile acids, which are elevated after surgery, can trigger PYY release not only from enteroendocrine cells but also from human pancreatic islets. In addition, we identify IL-22 as a new factor which is modulated by bariatric surgery in humans and which directly regulates PYY expression and release. Interpretation: This study shows that some major metabolic benefits of bariatric surgery can be emulated ex vivo. Our findings are expected to have a direct impact on the development of new non-surgical therapy for T2D correction. Keywords: Bariatric surgery, Diabetes, PYY, IL-22, Gut hormones, Pancreatic hormone secretion
