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

被引：128

作者：

Larraufie, Pierre ^{[1
]}

Roberts, Geoffrey P. ^{[1
]}

McGavigan, Anne K. ^{[1
]}

Kay, Richard G. ^{[1
]}

Li, Joyce ^{[2
]}

Leiter, Andrew ^{[2
]}

Melvin, Audrey ^{[1
]}

Biggs, Emma K. ^{[1
]}

Ravn, Peter ^{[3
]}

Davy, Kathleen ^{[4
]}

Hornigold, David C. ^{[4
]}

Yeo, Giles S. H. ^{[1
]}

Hardwick, Richard H. ^{[5
]}

Reimann, Frank ^{[1
]}

Gribble, Fiona M. ^{[1
]}

机构：

[1] Addenbrookes Hosp, Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Hills Rd, Cambridge CB2 0QQ, England

[2] Univ Massachusetts, Dept Med, Sch Med, Worcester, MA 01605 USA

[3] MedImmune, Dept Antibody Discovery & Prot Engn, Granta Pk, Cambridge CB21 6GH, England

[4] MedImmune, Dept Cardiovasc & Metab Dis, Granta Pk, Cambridge, England

[5] Addenbrookes Hosp, Cambridge Oesophagogastr Ctr, Cambridge, England

来源：

CELL REPORTS | 2019年 / 26卷 / 06期

基金：

英国惠康基金;

关键词：

GLUCAGON-LIKE PEPTIDE-1; Y GASTRIC BYPASS; ENTEROENDOCRINE CELLS; SECRETION; TOLERANCE; HORMONE; HYPOGLYCEMIA; METABOLISM; FAT;

D O I：

10.1016/j.celrep.2019.01.047

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Bariatric surgery is widely used to treat obesity and 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 debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) 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; 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.

引用

页码：1399 / +

页数：16

共 43 条

[1] Development and characterisation of a novel glucagon like peptide-1 receptor antibody [J].

Biggs, Emma K. ;

Liang, Lihuan ;

Naylor, Jacqueline ;

Madalli, Shimona ;

Collier, Rachel ;

Coghlan, Matthew P. ;

Baker, David J. ;

Hornigold, David C. ;

Ravn, Peter ;

Reimann, Frank ;

Gribble, Fiona M. .

DIABETOLOGIA, 2018, 61 (03) :711-721

[2] Co-storage and release of insulin-like peptide-5, glucagon-like peptide-1 and peptideYY from murine and human colonic enteroendocrine cells [J].

Billing, Lawrence J. ;

Smith, Christopher A. ;

Larraufie, Pierre ;

Goldspink, Deborah A. ;

Galvin, Sam ;

Kay, Richard G. ;

Howe, Jonathan D. ;

Walker, Ryan ;

Pruna, Mihai ;

Glass, Leslie ;

Pais, Ramona ;

Gribble, Fiona M. ;

Reimann, Frank .

MOLECULAR METABOLISM, 2018, 16 :65-75

[3] The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice [J].

Chambers, Adam ;

Sorrell, Joyce ;

Haller, April ;

Roelofs, Karen ;

Hutch, Chelsea ;

Kim, Ki-Suk ;

Gutierrez-Aguilar, Ruth ;

Li, Bailing ;

Drucker, Daniel ;

DAlessio, David ;

Seeley, Randy ;

Sandoval, Darleen .

CELL METABOLISM, 2017, 25 (04) :927-+

[4] Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia [J].

Craig, Colleen M. ;

Liu, Li-Fen ;

Deacon, Carolyn F. ;

Holst, Jens J. ;

McLaughlin, Tracey L. .

DIABETOLOGIA, 2017, 60 (03) :531-540

[5] Postprandial Diabetic Glucose Tolerance Is Normalized by Gastric Bypass Feeding as Opposed to Gastric Feeding and Is Associated With Exaggerated GLP-1 Secretion - A case report [J].

Dirksen, Carsten ;

Hansen, Dorte L. ;

Madsbad, Sten ;

Hvolris, Lisbeth E. ;

Naver, Lars S. ;

Holst, Jens J. ;

Worm, Dorte .

DIABETES CARE, 2010, 33 (02) :375-377

[6] STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

[7] GLP-1 Effects on Islets: Hormonal, Neuronal, or Paracrine? [J].

Donath, Marc Y. ;

Burcelin, Remy .

DIABETES CARE, 2013, 36 :S145-S148

[8] Enhanced Glucose Control Following Vertical Sleeve Gastrectomy Does Not Require a β-Cell Glucagon-Like Peptide 1 Receptor [J].

Douros, Jonathan D. ;

Lewis, Alfor G. ;

Smith, Eric P. ;

Niu, JingJing ;

Capozzi, Megan ;

Wittmann, April ;

Campbell, Jonathan ;

Tong, Jenny ;

Wagner, Constance ;

Mahbod, Parinaz ;

Seeley, Randy ;

D'Alessio, David A. .

DIABETES, 2018, 67 (08) :1504-1511

[9] β-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose Tolerance After Vertical Sleeve Gastrectomy [J].

Garibay, Darline ;

McGavigan, Anne K. ;

Lee, Seon A. ;

Ficorilli, James V. ;

Cox, Amy L. ;

Michael, M. Dodson ;

Sloop, Kyle W. ;

Cummings, Bethany P. .

ENDOCRINOLOGY, 2016, 157 (09) :3405-3409

[10] Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium [J].

Gribble, Fiona M. ;

Reimann, Frank .

ANNUAL REVIEW OF PHYSIOLOGY, VOL 78, 2016, 78 :277-299

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