PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context
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 tyros...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-02-01
|
| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418306170 |
| id |
doaj-71c6b79f837b45f38e9de4a65a371865 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context EBioMedicine |
| author_facet |
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 |
| author_sort |
Claudia Guida |
| title |
PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context |
| title_short |
PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context |
| title_full |
PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context |
| title_fullStr |
PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context |
| title_full_unstemmed |
PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in context |
| title_sort |
pyy plays a key role in the resolution of diabetes following bariatric surgery in humansresearch in context |
| publisher |
Elsevier |
| series |
EBioMedicine |
| issn |
2352-3964 |
| publishDate |
2019-02-01 |
| description |
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 |
| url |
http://www.sciencedirect.com/science/article/pii/S2352396418306170 |
| work_keys_str_mv |
AT claudiaguida pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT samdstephen pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT michaelwatson pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT nialldempster pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT pierrelarraufie pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT thomasmarjot pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT tamsincargill pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT lisarickers pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT michaelpavlides pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT jeremytomlinson pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT jeremyflcobbold pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT chunmeizhao pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT duanchen pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT fionagribble pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT frankreimann pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT richardgillies pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT brunosgromo pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT patrikrorsman pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT johndryan pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext AT reshmadramracheya pyyplaysakeyroleintheresolutionofdiabetesfollowingbariatricsurgeryinhumansresearchincontext |
| _version_ |
1724968711561936896 |
| spelling |
doaj-71c6b79f837b45f38e9de4a65a3718652020-11-25T01:58:42ZengElsevierEBioMedicine2352-39642019-02-01406776PYY plays a key role in the resolution of diabetes following bariatric surgery in humansResearch in contextClaudia Guida0Sam D. Stephen1Michael Watson2Niall Dempster3Pierre Larraufie4Thomas Marjot5Tamsin Cargill6Lisa Rickers7Michael Pavlides8Jeremy Tomlinson9Jeremy F.L. Cobbold10Chun-Mei Zhao11Duan Chen12Fiona Gribble13Frank Reimann14Richard Gillies15Bruno Sgromo16Patrik Rorsman17John D. Ryan18Reshma D. Ramracheya19Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UKTranslational Gastroenterology Unit, University of Oxford, Oxford, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UKMetabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UKTranslational Gastroenterology Unit, University of Oxford, Oxford, UKTranslational Gastroenterology Unit, University of Oxford, Oxford, UKOxford Bariatric Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UKOxford Centre for Clinical Magnetic Resonance Research, University of Oxford, UK; Oxford NIHR Biomedical Research Centre, Oxford, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UKTranslational Gastroenterology Unit, University of Oxford, Oxford, UKDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayDepartment of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, NorwayMetabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UKMetabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UKOxford Bariatric Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UKOxford Bariatric Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UKOxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UKTranslational Gastroenterology Unit, University of Oxford, Oxford, UK; Correspondence to: J. D. Ryan, Translational Gastroenterology Unit, University of Oxford, Oxford, UK.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 secretionhttp://www.sciencedirect.com/science/article/pii/S2352396418306170 |