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

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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 & 3 andre Jacob 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 increases in circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1).

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

DESIGN AND SETTING: Sub-study 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 gastrointestinal mucosal biopsy retrieval. Mixed meal tests were performed 1 week and 3 months before and after RYGB.

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

RESULTS: We observed increased postprandial plasma concentrations of glucagon after RYGB. Small intestinal expression of the glucagon gene increased after surgery. Glucagon was identified in the small intestinal biopsies obtained after, but not before RYGB. Immunohistochemically, mucosal biopsies from the small intestine harbored cells co-staining for GLP-1 and immuno-reactive glucagon.

CONCLUSIONS: Increased concentrations of glucagon, estimated by two glucagon specific assays, were observed in small intestinal biopsies and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically co-staining for GLP-1 and glucagon-like immunoreactivity after RYGB. These findings suggest that glucagon derived from small intestinal enteroendocrine L-cells may contribute to postprandial plasma concentrations of glucagon after RYGB.

OriginalsprogEngelsk
TidsskriftThe Journal of clinical endocrinology and metabolism
ISSN0021-972X
DOI
StatusE-pub ahead of print - 5 jul. 2019

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Copyright © 2019 Endocrine Society.

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