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.
Highlights
Gastroenteropancreatic neuroendocrine tumours are rare with an annual incidence rate of less than 10 per million population [1]
The vast majority of proglucagon-expressing tumours are sporadic (80 ) with the remainder associated with Multiple Endocrine Neoplasia-type 1 (MEN1), an inherited tumour predisposition syndrome, or Mahvash disease, an extremely rare cause of familial pancreatic α-cell hyperplasia and Nicolai Jacob Wewer Albrechtsen, et al.: Do glucagonomas always produce glucagon?
GLP-1 and glucagon both promote negative energy balance which may result in profound weight loss in pathological states, such as in the glucagonoma syndrome, when these peptide hormones may be secreted at high levels
Summary
Gastroenteropancreatic neuroendocrine tumours are rare with an annual incidence rate of less than 10 per million population [1]. Clinical manifestations of proglucagon-expressing tumours exhibit marked phenotypic variation possibly due to heterogeneity of their secreted peptide repertoire. Glucagonomas arise mostly from pathological transformation of pancreatic islet α-cells that synthesise and secrete proglucagon-derived peptides (Figure 1).
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