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

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

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

SN - 0021-972X

VL - 104

SP - 6403

EP - 6416

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 12

ER -