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


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.

TidsskriftThe Journal of clinical endocrinology and metabolism
Udgave nummer12
Sider (fra-til)6403-6416
Antal sider14
StatusUdgivet - 1 dec. 2019


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