Do glucagonomas always produce glucagon?

Nicolai Jacob Wewer Albrechtsen; Benjamin Challis; Ivan Damjanov; Jens Juul Holst

doi:10.17305/bjbms.2015.794

Authors

Nicolai Jacob Wewer Albrechtsen 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 http://orcid.org/0000-0003-4230-5753
Benjamin Challis University of Cambridge Wellcome Trust-MRC Institute of Metabolic Science and University of Cambridge, Cambridge, CB2 0QQ, UK Wolfson Diabetes and Endocrinology Clinic, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Cambridge, CB2 0QQ
Ivan Damjanov Department of Pathology and Laboratory Medicine , The University of Kansas School of Medicine, Kansas City, KS, USA
Jens Juul Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark

DOI:

https://doi.org/10.17305/bjbms.2015.794

Keywords:

Glucagonoma, neuroendocrine tumours, NETs, hyperglucagonemia, GLP-1, Proglucagon

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.

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Author Biography

Nicolai Jacob Wewer Albrechtsen, 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

Medical Doctor at University of Copenhagen, PhD Student
GCSRT at Harvard Medical School,
Member of Harvard Alumni

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