Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery

Bariatri og Diabetes

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

CONTEXT: After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1).

OBJECTIVE: To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut.

DESIGN AND SETTING: Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark.

PARTICIPANTS: Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes.

INTERVENTIONS: Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB.

MAIN OUTCOME MEASURES: The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry.

RESULTS: Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon.

CONCLUSION: Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number12
Pages (from-to)6403-6416
ISSN0021-972X
DOIs
Publication statusPublished - 1. Dec 2019

Fingerprint

Gastric Bypass
Glucagon
Surgery
Biopsy
Small Intestine
Plasmas
Glucagon-Like Peptide 1
Enteroendocrine Cells
Denmark
Medical problems
Immunoassay
Type 2 Diabetes Mellitus
Mass spectrometry
Meals
Cross-Sectional Studies
Genes
Monoclonal Antibodies
Hormones
Insulin

Cite this

@article{742a8aa9ce32477284a50e133be4cd71,
title = "Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery",
abstract = "CONTEXT: After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1).OBJECTIVE: To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut.DESIGN AND SETTING: Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark.PARTICIPANTS: Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes.INTERVENTIONS: Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB.MAIN OUTCOME MEASURES: The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry.RESULTS: Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon.CONCLUSION: Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.",
author = "Tina Jorsal and {Wewer Albrechtsen}, {Nicolai J} and Christensen, {Marie M} and Brynjulf Mortensen and Erik Wandall and Ebbe Langholz and Steffen Friis and Dorte Worm and Cathrine {\O}rskov and St{\o}ving, {Ren{\'e} K} and Alin Andries and Juhl, {Claus B} and Frederik S{\o}rensen and Forman, {Julie L} and Mechthilde Falkenhahn and Musholt, {Petra B} and Stefan Theis and Larsen, {Philip J} and Holst, {Jens J} and Niels Vrang and Jacob Jelsing and Tina Vilsb{\o}ll and Knop, {Filip K} and {Bariatri og Diabetes}",
note = "Copyright {\circledC} 2019 Endocrine Society.",
year = "2019",
month = "12",
day = "1",
doi = "10.1210/jc.2019-00062",
language = "English",
volume = "104",
pages = "6403--6416",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Heinemann",
number = "12",

}

Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery. / Bariatri og Diabetes.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 12, 01.12.2019, p. 6403-6416.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery

AU - Jorsal, Tina

AU - Wewer Albrechtsen, Nicolai J

AU - Christensen, Marie M

AU - Mortensen, Brynjulf

AU - Wandall, Erik

AU - Langholz, Ebbe

AU - Friis, Steffen

AU - Worm, Dorte

AU - Ørskov, Cathrine

AU - Støving, René K

AU - Andries, Alin

AU - Juhl, Claus B

AU - Sørensen, Frederik

AU - Forman, Julie L

AU - Falkenhahn, Mechthilde

AU - Musholt, Petra B

AU - Theis, Stefan

AU - Larsen, Philip J

AU - Holst, Jens J

AU - Vrang, Niels

AU - Jelsing, Jacob

AU - Vilsbøll, Tina

AU - Knop, Filip K

AU - Bariatri og Diabetes

N1 - Copyright © 2019 Endocrine Society.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - CONTEXT: After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1).OBJECTIVE: To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut.DESIGN AND SETTING: Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark.PARTICIPANTS: Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes.INTERVENTIONS: Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB.MAIN OUTCOME MEASURES: The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry.RESULTS: Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon.CONCLUSION: Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

AB - CONTEXT: After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1).OBJECTIVE: To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut.DESIGN AND SETTING: Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark.PARTICIPANTS: Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes.INTERVENTIONS: Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB.MAIN OUTCOME MEASURES: The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry.RESULTS: Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon.CONCLUSION: Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

U2 - 10.1210/jc.2019-00062

DO - 10.1210/jc.2019-00062

M3 - Journal article

C2 - 31276156

VL - 104

SP - 6403

EP - 6416

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -