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Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery

43 Pages Posted: 14 Nov 2018 Sneak Peek Status: Under Review

See all articles by Pierre Larraufie

Pierre Larraufie

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Geoffrey P. Roberts

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Anne McGavigan

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Richard G. Kay

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Joyce Li

University of Massachusetts Worcester - Department of Medicine

Andrew Leiter

University of Massachusetts Worcester - Department of Medicine

Audrey Melvin

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Emma K. Biggs

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Peter Ravn

MedImmune Ltd. - Department of Antibody Discovery and Protein Engineering

Kathleen Davy

MedImmune Ltd. - Department of Cardiovascular and Metabolic Disease

David Hornigold

MedImmune Ltd. - Department of Cardiovascular and Metabolic Disease

Giles Yeo

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Richard H. Hardwick

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge Oesophago-Gastric Centre

Frank Reimann

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Fiona Gribble

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

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Abstract

Bariatric surgery is widely used to treat obesity, and additionally improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide-YY (PYY) and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains hotly debated. Here we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1R) post-gastrectomy in lean humans using Exendin-9, or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery, but instead we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut, and is a key driver of enhanced insulin secretion.

Suggested Citation

Larraufie, Pierre and Roberts, Geoffrey P. and McGavigan, Anne and Kay, Richard G. and Li, Joyce and Leiter, Andrew and Melvin, Audrey and Biggs, Emma K. and Ravn, Peter and Davy, Kathleen and Hornigold, David and Yeo, Giles and Hardwick, Richard H. and Reimann, Frank and Gribble, Fiona, Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery (November 13, 2018). Available at SSRN: https://ssrn.com/abstract=3283706 or http://dx.doi.org/10.2139/ssrn.3283706
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Pierre Larraufie

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Geoffrey P. Roberts

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Anne McGavigan

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Richard G. Kay

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Joyce Li

University of Massachusetts Worcester - Department of Medicine

55 Lake Avenue North
Worcester, MA 01655
United States

Andrew Leiter

University of Massachusetts Worcester - Department of Medicine

55 Lake Avenue North
Worcester, MA 01655
United States

Audrey Melvin

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Emma K. Biggs

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Peter Ravn

MedImmune Ltd. - Department of Antibody Discovery and Protein Engineering

Granta Park
Cambridge, CB21 6GH
United Kingdom

Kathleen Davy

MedImmune Ltd. - Department of Cardiovascular and Metabolic Disease

Granta Park
Cambridge, CB21 6GH
United Kingdom

David Hornigold

MedImmune Ltd. - Department of Cardiovascular and Metabolic Disease

Granta Park
Cambridge, CB21 6GH
United Kingdom

Giles Yeo

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Richard H. Hardwick

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge Oesophago-Gastric Centre

Cambridge, CB2 0QQ
United Kingdom

Frank Reimann

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories ( email )

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

Fiona Gribble (Contact Author)

NHS Foundation Trust, Cambridge University Hospitals, Addenbrooke's Hospital, Wellcome Trust MRC Institute of Metabolic Science, Metabolic Research Laboratories ( email )

Hills Road
Box 289, Addenbrooke’s Hospital
Cambridge, CB2 0QQ
United Kingdom

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