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Diabetes. 2016 Mar;65(3):585-97. doi: 10.2337/db15-1541. Epub 2015 Dec 15.

Evidence of Extrapancreatic Glucagon Secretion in Man.

Author information

1
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.
2
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.
3
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
4
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.
5
Center for Pregnant Women with Diabetes, Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
6
Department of Gastrointestinal Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
7
Clinical Metabolomics Core Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
8
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
9
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
10
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.
11
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.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02006459.

Comment in

PMID:
26672094
DOI:
10.2337/db15-1541
[Indexed for MEDLINE]
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