title: Evidence of Extrapancreatic Glucagon Secretion in Man.
abstract: Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from α-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry-based proteomics) and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Asger
authors.initials: A
authors.lastname: Lund
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonatan I
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Nicolai J
authors.initials: NJ
authors.lastname: Wewer Albrechtsen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Christensen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Magnus
authors.initials: M
authors.lastname: Grøndahl
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Center for Pregnant Women with Diabetes, Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Mathiesen
authors.affiliation: Department of Gastrointestinal Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten P
authors.initials: CP
authors.lastname: Hansen
authors.affiliation: Department of Gastrointestinal Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Storkholm
authors.affiliation: Clinical Metabolomics Core Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hornburg
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Meissner
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany The Novo Nordisk Foundation Center for Protein Research, Proteomics Program, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Larsen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark filipknop@dadlnet.dk.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D002766:Cholecystokinin / Q000378:metabolism; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000601:surgery*; D010195:Pancreatitis / Q000601:surgery*; D010446:Peptide Fragments / Q000378:metabolism; D040901:Proteomics; D011863:Radioimmunoassay; D053719:Tandem Mass Spectrometry
chemical_list: D001786:Blood Glucose; D005755:Gastrins; D010446:Peptide Fragments; C549099:gastric inhibitory polypeptide (1-30); D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002766:Cholecystokinin; D005947:Glucose