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

Tina Jorsal; Nicolai J Wewer Albrechtsen; Marie M Christensen; Brynjulf Mortensen; Erik Wandall; Ebbe Langholz; Steffen Friis; Dorte Worm; Cathrine Ørskov; René K Støving; Alin Andries; Claus B Juhl; Frederik Sørensen; Julie L Forman; Mechthilde Falkenhahn; Petra B Musholt; Stefan Theis; Philip J Larsen; Jens J Holst; Niels Vrang; Jacob Jelsing; Tina Vilsbøll; Filip K Knop

doi:10.1210/jc.2019-00062

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

Tina Jorsal, Nicolai J Wewer Albrechtsen, Marie M Christensen, Brynjulf Mortensen, Erik Wandall, Ebbe Langholz, Steffen Friis, Dorte Worm, Cathrine Ørskov, René K Støving, Alin Andries, Claus B Juhl, Frederik Sørensen, Julie L Forman, Mechthilde Falkenhahn, Petra B Musholt, Stefan Theis, Philip J Larsen, Jens J Holst, Niels VrangJacob Jelsing, Tina Vilsbøll, Filip K Knop^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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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 language	English
Journal	The Journal of Clinical Endocrinology & Metabolism
Volume	104
Issue number	12
Pages (from-to)	6403-6416
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2019-00062
Publication status	Published - 1. Dec 2019

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10.1210/jc.2019-00062

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Jorsal, T., Wewer Albrechtsen, N. J., Christensen, M. M., Mortensen, B., Wandall, E., Langholz, E., Friis, S., Worm, D., Ørskov, C., Støving, R. K., Andries, A., Juhl, C. B., Sørensen, F., Forman, J. L., Falkenhahn, M., Musholt, P. B., Theis, S., Larsen, P. J., Holst, J. J., ... Knop, F. K. (2019). Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery. The Journal of Clinical Endocrinology & Metabolism, 104(12), 6403-6416. https://doi.org/10.1210/jc.2019-00062

@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}",

note = "Copyright {\textcopyright} 2019 Endocrine Society.",

year = "2019",

month = dec,

day = "1",

doi = "10.1210/jc.2019-00062",

language = "English",

volume = "104",

pages = "6403--6416",

journal = "The Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "12",

}

Jorsal, T, Wewer Albrechtsen, NJ, Christensen, MM, Mortensen, B, Wandall, E, Langholz, E, Friis, S, Worm, D, Ørskov, C, Støving, RK, Andries, A, Juhl, CB, Sørensen, F, Forman, JL, Falkenhahn, M, Musholt, PB, Theis, S, Larsen, PJ, Holst, JJ, Vrang, N, Jelsing, J, Vilsbøll, T & Knop, FK 2019, 'Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery', The Journal of Clinical Endocrinology & Metabolism, vol. 104, no. 12, pp. 6403-6416. https://doi.org/10.1210/jc.2019-00062

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

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

SN - 0021-972X

VL - 104

SP - 6403

EP - 6416

JO - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

IS - 12

ER -

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

Abstract

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