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

Autor:	Jorsal T; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Steno Diabetes Center Copenhagen, Gentofte, Denmark., Wewer Albrechtsen NJ; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Christensen MM; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Steno Diabetes Center Copenhagen, Gentofte, Denmark., Mortensen B; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Wandall E; Endoscopic Unit, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Langholz E; Endoscopic Unit, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Friis S; Endoscopic Unit, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark., Worm D; Department of Medicine, Amager Hospital, University of Copenhagen, Copenhagen, Denmark., Ørskov C; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Støving RK; Elite Research Center for Medical Endocrinology & Center for Eating Disorders, Odense University Hospital, Odense, Denmark., Andries A; Surgical Unit, Sydvestjysk Sygehus, Esbjerg, Denmark., Juhl CB; Surgical Unit, Sydvestjysk Sygehus, Esbjerg, Denmark., Sørensen F; Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark., Forman JL; Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark., Falkenhahn M; Sanofi Aventis, Frankfurt, Germany., Musholt PB; Sanofi Aventis, Frankfurt, Germany., Theis S; Sanofi Aventis, Frankfurt, Germany., Larsen PJ; Sanofi Aventis, Frankfurt, Germany., Holst JJ; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Vrang N; Gubra, Hørsholm, Denmark., Jelsing J; Gubra, Hørsholm, Denmark., Vilsbøll T; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Steno Diabetes Center Copenhagen, Gentofte, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Knop FK; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.; Steno Diabetes Center Copenhagen, Gentofte, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2019 Dec 01; Vol. 104 (12), pp. 6403-6416.
DOI:	10.1210/jc.2019-00062
Abstrakt:	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. (Copyright © 2019 Endocrine Society.)
Databáze:	MEDLINE
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