title: Do glucagonomas always produce glucagon?
abstract: Pancreatic islet α-cell tumours that overexpress proglucagon are typically associated with the glucagonoma syndrome, a rare disease entity characterised by necrolytic migratory erythema, impaired glucose tolerance, thromboembolic complications and psychiatric disturbances. Paraneoplastic phenomena associated with enteric overexpression of proglucagon-derived peptides are less well recognized and include gastrointestinal dysfunction and hyperinsulinaemic hypoglycaemia. The diverse clinical manifestations associated with glucagon-expressing tumours can be explained, in part, by the repertoire of tumorally secreted peptides liberated through differential post-translational processing of tumour-derived proglucagon. Proglucagon-expressing tumours may be divided into two broad biochemical subtypes defined by either secretion of glucagon or GLP-1, GLP-2 and the glucagon-containing peptides, glicentin and oxyntomodulin, due to an islet α-cell or enteroendocrine L-cell pattern of proglucagon processing, respectively. In the current review we provide an updated overview of the clinical presentation of proglucagon-expressing tumours in relation to known physiological actions of proglucagon-derived peptides and suggest that detailed biochemical characterisation of the peptide repertoire secreted from these tumours may provide new opportunities for diagnosis and clinical management.
authors.affiliation: 1: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark 2: Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. hgk795@ku.dk.
authors.forename: Nicolai Jacob
authors.initials: NJ
authors.lastname: Wewer Albrechtsen
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Challis
authors.forename: Ivan
authors.initials: I
authors.lastname: Damjanov
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000818:Animals; D005767:Gastrointestinal Diseases / Q000378:metabolism; D005786:Gene Expression Regulation; D053771:Glicentin / Q000378:metabolism; D005934:Glucagon / Q000096:biosynthesis*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D005935:Glucagonoma / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D053772:Oxyntomodulin / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010446:Peptide Fragments; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D052336:Proglucagon / Q000378:metabolism; D000072417:Protein Domains
chemical_list: D053772:Oxyntomodulin; D010446:Peptide Fragments; D010455:Peptides; D052336:Proglucagon; D053771:Glicentin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon