Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides

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Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides. / Challis, Benjamin G; Albrechtsen, Nicolai J Wewer; Bansiya, Vishakha; Burling, Keith; Barker, Peter; Hartmann, Bolette; Gribble, Fiona; O'Rahilly, Stephen; Holst, Jens J; Simpson, Helen L.

In: Endocrinology, Diabetes & Metabolism Case Reports, Vol. 2015, 150105, 2015, p. 1-7.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Challis, BG, Albrechtsen, NJW, Bansiya, V, Burling, K, Barker, P, Hartmann, B, Gribble, F, O'Rahilly, S, Holst, JJ & Simpson, HL 2015, 'Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides', Endocrinology, Diabetes & Metabolism Case Reports, vol. 2015, 150105, pp. 1-7. https://doi.org/10.1530/EDM-15-0105

APA

Challis, B. G., Albrechtsen, N. J. W., Bansiya, V., Burling, K., Barker, P., Hartmann, B., Gribble, F., O'Rahilly, S., Holst, J. J., & Simpson, H. L. (2015). Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides. Endocrinology, Diabetes & Metabolism Case Reports, 2015, 1-7. [150105]. https://doi.org/10.1530/EDM-15-0105

Vancouver

Challis BG, Albrechtsen NJW, Bansiya V, Burling K, Barker P, Hartmann B et al. Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides. Endocrinology, Diabetes & Metabolism Case Reports. 2015;2015:1-7. 150105. https://doi.org/10.1530/EDM-15-0105

Author

Challis, Benjamin G ; Albrechtsen, Nicolai J Wewer ; Bansiya, Vishakha ; Burling, Keith ; Barker, Peter ; Hartmann, Bolette ; Gribble, Fiona ; O'Rahilly, Stephen ; Holst, Jens J ; Simpson, Helen L. / Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides. In: Endocrinology, Diabetes & Metabolism Case Reports. 2015 ; Vol. 2015. pp. 1-7.

Bibtex

@article{4f369ed2411341099a751f06b8539a2f,
title = "Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides",
abstract = "UNLABELLED: Pancreatic neuroendocrine tumours (pNETs) secreting proglucagon are associated with phenotypic heterogeneity. Here, we describe two patients with pNETs and varied clinical phenotypes due to differential processing and secretion of proglucagon-derived peptides (PGDPs). Case 1, a 57-year-old woman presented with necrolytic migratory erythema, anorexia, constipation and hyperinsulinaemic hypoglycaemia. She was found to have a grade 1 pNET, small bowel mucosal thickening and hyperglucagonaemia. Somatostatin analogue (SSA) therapy improved appetite, abolished hypoglycaemia and improved the rash. Case 2, a 48-year-old male presented with diabetes mellitus, diarrhoea, weight loss, nausea, vomiting and perineal rash due to a grade 1 metastatic pNET and hyperglucagonaemia. In both cases, plasma levels of all measured PGDPs were elevated and attenuated following SSA therapy. In case 1, there was increased production of intact glucagon-like peptide 1 (GLP-1) and GLP-2, similar to that of the enteroendocrine L cell. In case 2, pancreatic glucagon was elevated due to a pancreatic α-cell-like proglucagon processing profile. In summary, we describe two patients with pNETs and heterogeneous clinical phenotypes due to differential processing and secretion of PGDPs. This is the first description of a patient with symptomatic hyperinsulinaemic hypoglycaemia and marked gastrointestinal dysfunction due to, in part, a proglucagon-expressing pNET.LEARNING POINTS: PGDPs exhibit a diverse range of biological activities including critical roles in glucose and amino acid metabolism, energy homeostasis and gastrointestinal physiology.The clinical manifestations of proglucagon-expressing tumours may exhibit marked phenotypic variation due to the biochemical heterogeneity of their secreted peptide repertoire.Specific and precise biochemical assessment of individuals with proglucagon-expressing tumours may provide opportunities for improved diagnosis and clinical management.",
author = "Challis, {Benjamin G} and Albrechtsen, {Nicolai J Wewer} and Vishakha Bansiya and Keith Burling and Peter Barker and Bolette Hartmann and Fiona Gribble and Stephen O'Rahilly and Holst, {Jens J} and Simpson, {Helen L}",
year = "2015",
doi = "10.1530/EDM-15-0105",
language = "English",
volume = "2015",
pages = "1--7",
journal = "Endocrinology, Diabetes & Metabolism Case Reports",
issn = "2052-0573",
publisher = "BioScientifica Ltd.",

}

RIS

TY - JOUR

T1 - Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides

AU - Challis, Benjamin G

AU - Albrechtsen, Nicolai J Wewer

AU - Bansiya, Vishakha

AU - Burling, Keith

AU - Barker, Peter

AU - Hartmann, Bolette

AU - Gribble, Fiona

AU - O'Rahilly, Stephen

AU - Holst, Jens J

AU - Simpson, Helen L

PY - 2015

Y1 - 2015

N2 - UNLABELLED: Pancreatic neuroendocrine tumours (pNETs) secreting proglucagon are associated with phenotypic heterogeneity. Here, we describe two patients with pNETs and varied clinical phenotypes due to differential processing and secretion of proglucagon-derived peptides (PGDPs). Case 1, a 57-year-old woman presented with necrolytic migratory erythema, anorexia, constipation and hyperinsulinaemic hypoglycaemia. She was found to have a grade 1 pNET, small bowel mucosal thickening and hyperglucagonaemia. Somatostatin analogue (SSA) therapy improved appetite, abolished hypoglycaemia and improved the rash. Case 2, a 48-year-old male presented with diabetes mellitus, diarrhoea, weight loss, nausea, vomiting and perineal rash due to a grade 1 metastatic pNET and hyperglucagonaemia. In both cases, plasma levels of all measured PGDPs were elevated and attenuated following SSA therapy. In case 1, there was increased production of intact glucagon-like peptide 1 (GLP-1) and GLP-2, similar to that of the enteroendocrine L cell. In case 2, pancreatic glucagon was elevated due to a pancreatic α-cell-like proglucagon processing profile. In summary, we describe two patients with pNETs and heterogeneous clinical phenotypes due to differential processing and secretion of PGDPs. This is the first description of a patient with symptomatic hyperinsulinaemic hypoglycaemia and marked gastrointestinal dysfunction due to, in part, a proglucagon-expressing pNET.LEARNING POINTS: PGDPs exhibit a diverse range of biological activities including critical roles in glucose and amino acid metabolism, energy homeostasis and gastrointestinal physiology.The clinical manifestations of proglucagon-expressing tumours may exhibit marked phenotypic variation due to the biochemical heterogeneity of their secreted peptide repertoire.Specific and precise biochemical assessment of individuals with proglucagon-expressing tumours may provide opportunities for improved diagnosis and clinical management.

AB - UNLABELLED: Pancreatic neuroendocrine tumours (pNETs) secreting proglucagon are associated with phenotypic heterogeneity. Here, we describe two patients with pNETs and varied clinical phenotypes due to differential processing and secretion of proglucagon-derived peptides (PGDPs). Case 1, a 57-year-old woman presented with necrolytic migratory erythema, anorexia, constipation and hyperinsulinaemic hypoglycaemia. She was found to have a grade 1 pNET, small bowel mucosal thickening and hyperglucagonaemia. Somatostatin analogue (SSA) therapy improved appetite, abolished hypoglycaemia and improved the rash. Case 2, a 48-year-old male presented with diabetes mellitus, diarrhoea, weight loss, nausea, vomiting and perineal rash due to a grade 1 metastatic pNET and hyperglucagonaemia. In both cases, plasma levels of all measured PGDPs were elevated and attenuated following SSA therapy. In case 1, there was increased production of intact glucagon-like peptide 1 (GLP-1) and GLP-2, similar to that of the enteroendocrine L cell. In case 2, pancreatic glucagon was elevated due to a pancreatic α-cell-like proglucagon processing profile. In summary, we describe two patients with pNETs and heterogeneous clinical phenotypes due to differential processing and secretion of PGDPs. This is the first description of a patient with symptomatic hyperinsulinaemic hypoglycaemia and marked gastrointestinal dysfunction due to, in part, a proglucagon-expressing pNET.LEARNING POINTS: PGDPs exhibit a diverse range of biological activities including critical roles in glucose and amino acid metabolism, energy homeostasis and gastrointestinal physiology.The clinical manifestations of proglucagon-expressing tumours may exhibit marked phenotypic variation due to the biochemical heterogeneity of their secreted peptide repertoire.Specific and precise biochemical assessment of individuals with proglucagon-expressing tumours may provide opportunities for improved diagnosis and clinical management.

U2 - 10.1530/EDM-15-0105

DO - 10.1530/EDM-15-0105

M3 - Journal article

C2 - 26693280

VL - 2015

SP - 1

EP - 7

JO - Endocrinology, Diabetes & Metabolism Case Reports

JF - Endocrinology, Diabetes & Metabolism Case Reports

SN - 2052-0573

M1 - 150105

ER -

ID: 152286555