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  • Investigating Intestinal Glucagon After Roux-en-Y Gastric Bypass Surgery.

Investigating Intestinal Glucagon After Roux-en-Y Gastric Bypass Surgery.

The Journal of clinical endocrinology and metabolism (2019-07-06)
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
ABSTRACT

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). To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut. Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark. Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes. 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. 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. 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. 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.

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Albumin, Human Serum, Fraction V, Low Heavy Metals